Updated on 2024/06/12

写真a

 
SUGA Hidetaka
 
Organization
Graduate School of Medicine Program in Integrated Medicine Internal Medicine Associate professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Associate professor

Degree 1

  1. 博士(医学) ( 2008.12   名古屋大学 ) 

Research Interests 5

  1. 糖尿病

  2. 再生医療

  3. 視床下部

  4. 内分泌

  5. 下垂体

Research Areas 3

  1. Life Science / Developmental biology

  2. Life Science / Metabolism and endocrinology

  3. Life Science / Metabolism and endocrinology

Current Research Project and SDGs 1

  1. 下垂体・視床下部の再生医療

Research History 8

  1. 名古屋大学未来社会創造機構   ナノライフシステム研究所・量子科学イノベーション研究所   准教授(兼任)

    2024.4

  2. Nagoya University   Part-time faculty member

    2022.2

  3. Nagoya University   Institute for Advanced Research   Associate Professor

    2022.2

  4. Nagoya University   Part-time faculty member

    2020.5

  5. Nagoya University   Graduate School of Medicine   Associate professor

    2019.4

  6. Nagoya University   Graduate School of Medicine   Lecturer

    2018.4 - 2019.3

  7. Nagoya University   Hospital, Hospital   Lecturer

    2017.4 - 2018.3

  8. Nagoya University   Hospital, Hospital   Assistant Professor

    2015.11 - 2017.3

▼display all

Education 3

  1. 名古屋大学大学院   医学系研究科博士課程

    2003.4 - 2007.3

  2. Nagoya University   Faculty of Medicine

    - 1999.3

      More details

    Country: Japan

  3. Nagoya University

    1993.4 - 1999.3

Professional Memberships 13

  1. 日本内科学会

  2. 日本内分泌学会

  3. 日本糖尿病学会

  4. 日本甲状腺学会

  5. 間脳下垂体腫瘍学会

  6. THE JAPANESE SOCIETY OF INTERNAL MEDICINE

  7. The Japan Endocrine Society

  8. 日本神経内分泌学会

  9. THE JAPAN DIABETES SOCIETY

  10. THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE

  11. 日本間脳下垂体腫瘍学会

  12. THE SOCIETY FOR CHEMISTRY AND MICRO-NANO SYSTEMS

  13. 日本甲状腺学会

▼display all

Awards 3

  1. 第33回日本神経内分泌学会川上賞

    2018.10   日本神経内分泌学会  

    須賀 英隆

     More details

    Award type:Award from Japanese society, conference, symposium, etc. 

  2. 第89回内分泌学会研究奨励賞

    2016.4   日本内分泌学会   多能性幹細胞を用いた視床下部・下垂体の分化誘導法開発研究

    須賀英隆

     More details

    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

  3. 研究奨励賞

    2009.1   バゾプレシン研究会   先天性腎性尿崩症に対する遺伝子治療法の開発

    須賀英隆, 長崎弘, 近藤貴昭, 椙村益久, 有馬寛, 大磯ユタカ

     More details

    Award type:Award from Japanese society, conference, symposium, etc.  Country:Japan

 

Papers 99

  1. Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study. Reviewed

    Kobayashi T, Iwama S, Yamagami A, Izuchi T, Suzuki K, Otake K, Yasuda Y, Ando M, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Hase T, Nishio N, Mori S, Shimokata T, Sano T, Niimi K, Yoshikawa N, Akamatsu S, Ando Y, Akiyama M, Sone M, Ishii M, Arima H

    Cancer immunology, immunotherapy : CII   Vol. 73 ( 8 ) page: 146   2024.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00262-024-03733-2

    PubMed

  2. Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells Reviewed

    Miwata T, Suga H, Mitsumoto K, Zhang J, Hamada Y, Sakakibara M, Soen M, Ozaki H, Asano T, Miyata T, Kawaguchi Y, Yasuda Y, Kobayashi T, Sugiyama M, Onoue T, Hagiwara D, Iwama S, Oyadomari S, Arima H

    Peptides   Vol. 173   page: 171151 - 171151   2024.3

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.peptides.2024.171151

    Web of Science

    PubMed

  3. Effects of Digitization of Self-Monitoring of Blood Glucose Records Using a Mobile App and the Cloud System on Outpatient Management of Diabetes: Single-Armed Prospective Study Reviewed

    Handa T, Onoue T, Kobayashi T, Maeda R, Mizutani K, Yamagami A, Kinoshita T, Yasuda Y, Iwama S, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Azuma Y, Kasai T, Yoshioka S, Kuwatsuka Y, Arima H

    JMIR Diabetes   Vol. 9   page: e48019 - e48019   2024.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JMIR Publications Inc.  

    Background

    In recent years, technologies promoting the digitization of self-monitoring of blood glucose (SMBG) records including app-cloud cooperation systems have emerged. Studies combining these technological interventions with support from remote health care professionals have reported improvements in glycemic control.

    Objective

    To assess the use of an app-cloud cooperation system linked with SMBG devices in clinical settings, we evaluated its effects on outpatient management of diabetes without remote health care professional support.

    Methods

    In this multicenter, open-label, and single-armed prospective study, 48 patients with diabetes (including type 1 and type 2) at 3 hospitals in Japan treated with insulin or glucagon-like peptide 1 receptor agonists and performing SMBG used the app-cloud cooperation system for 24 weeks. The SMBG data were automatically uploaded to the cloud via the app. The patients could check their data, and their attending physicians reviewed the data through the cloud prior to the patients’ regular visits. The primary outcome was changes in glycated hemoglobin (HbA1c) levels.

    Results

    Although HbA1c levels did not significantly change in all patients, the frequency of daily SMBG following applying the system was significantly increased before induction at 12 (0.60 per day, 95% CI 0.19-1.00; P=.002) and 24 weeks (0.43 per day, 95% CI 0.02-0.84; P=.04). In the subset of 21 patients whose antidiabetic medication had not been adjusted during the intervention period, a decrease in HbA1c level was observed at 12 weeks (P=.02); however, this significant change disappeared at 24 weeks (P=.49). The Diabetes Treatment Satisfaction Questionnaire total score and “Q4: convenience” and “Q5: flexibility” scores significantly improved after using the system (all P<.05), and 72% (33/46) patients and 76% (35/46) physicians reported that the app-cloud cooperation system helped them adjust insulin doses.

    Conclusions

    The digitization of SMBG records and sharing of the data by patients and attending physicians during face-to-face visits improved self-management in patients with diabetes.

    Trial Registration

    Japan Registry of Clinical Trials (jRCT) jRCTs042190057; https://jrct.niph.go.jp/en-latest-detail/jRCTs042190057

    DOI: 10.2196/48019

    PubMed

  4. Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade Reviewed

    Yamagami, A; Iwama, S; Kobayashi, T; Zhou, X; Yasuda, Y; Okuji, T; Ito, M; Izuchi, T; Ando, M; Onoue, T; Miyata, T; Sugiyama, M; Hagiwara, D; Suga, H; Banno, R; Arima, H

    ENDOCRINE JOURNAL   Vol. 71 ( 5 ) page: 515 - 526   2024

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1507/endocrj.EJ23-0480

    Web of Science

    PubMed

  5. Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial. Reviewed International journal

    Hayase A, Onoue T, Kobayashi T, Wada E, Handa T, Kinoshita T, Yamagami A, Yasuda Y, Iwama S, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Kuwatsuka Y, Ando M, Goto M, Arima H

    Primary care diabetes   Vol. 17 ( 6 ) page: 575 - 580   2023.12

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    AIMS: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. METHODS: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. RESULTS: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding "willingness to continue the current treatment" score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). CONCLUSIONS: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.

    DOI: 10.1016/j.pcd.2023.09.009

    Web of Science

    PubMed

  6. Touch imprint cytology is useful for the intraoperative pathological diagnosis of PitNETs’ surgical margins Reviewed

    Tanabe N, Inoshita N, Ishida A, Kato M, Yoshimoto H, Shiramizu H, Suga H, Tateno T, Ohashi K, Yamada S

    Brain Tumor Pathology   Vol. 40 ( 4 ) page: 215 - 221   2023.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Abstract

    Touch imprint cytology (TIC) and frozen section (FS) procedures are essential for intraoperative pathological diagnosis (IPD). They are invaluable tools for therapeutic decision-making, helping surgeons avoid under or overtreatment of patients. Pituitary neuroendocrine tumors (PitNETs) are generally small, slow-growing tumors with low-grade malignancy located at the base of the skull where it is impossible to maintain a wide tumor margin. Therefore, transsphenoidal surgery (TSS) should be performed with necessary caution, and with sufficient and minimal resection. Thus, this study aimed to evaluate the diagnostic accuracy of TIC for the diagnosis of PitNET and determine its ability to accurately evaluate the surgical margin compared to the FS procedure. A total of 104 fresh specimens from 28 patients who underwent TSS for PitNETs were examined using TIC and FS. TIC specimens were categorized according to the cell imprinting pattern. All specimens with a large number of neuroendocrine cells diffusely attached to the glass surfaces had PitNET components. Contrarily, no rich or diffuse cell attachments were observed in any non-tumoral endocrine cells. In conclusion, recognizing a pattern of endocrine cell adherence to glass is highly effective in IPD to certify the existence of a PitNET component.

    DOI: 10.1007/s10014-023-00470-9

    Web of Science

    PubMed

    Other Link: https://link.springer.com/article/10.1007/s10014-023-00470-9/fulltext.html

  7. Generation and purification of ACTH-secreting hPSC-derived pituitary cells for effective transplantation. Reviewed International journal

    Taga S., Suga H., Nakano T., Kuwahara A., Inoshita N., Kodani Y., Nagasaki H., Sato Y., Tsumura Y., Sakakibara M., Soen M., Miwata T., Ozaki H., Kano M., Watari K., Ikeda A., Yamanaka M., Takahashi Y., Kitamoto S., Kawaguchi Y., Miyata T., Kobayashi T., Sugiyama M., Onoue T., Yasuda Y., Hagiwara D., Iwama S., Tomigahara Y., Kimura T., Arima H.

    Stem cell reports   Vol. 18 ( 8 ) page: 1657 - 1671   2023.8

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Pituitary organoids are promising graft sources for transplantation in treatment of hypopituitarism. Building on development of self-organizing culture to generate pituitary-hypothalamic organoids (PHOs) using human pluripotent stem cells (hPSCs), we established techniques to generate PHOs using feeder-free hPSCs and to purify pituitary cells. The PHOs were uniformly and reliably generated through preconditioning of undifferentiated hPSCs and modulation of Wnt and TGF-β signaling after differentiation. Cell sorting using EpCAM, a pituitary cell-surface marker, successfully purified pituitary cells, reducing off-target cell numbers. EpCAM-expressing purified pituitary cells reaggregated to form three-dimensional pituitary spheres (3D-pituitaries). These exhibited high adrenocorticotropic hormone (ACTH) secretory capacity and responded to both positive and negative regulators. When transplanted into hypopituitary mice, the 3D-pituitaries engrafted, improved ACTH levels, and responded to in vivo stimuli. This method of generating purified pituitary tissue opens new avenues of research for pituitary regenerative medicine.

    DOI: 10.1016/j.stemcr.2023.05.002

    Web of Science

    PubMed

  8. Functional calcium- responsive parathyroid glands generated using single- step blastocyst complementation Reviewed International journal

    Kano M, Mizuno N, Sato H, Kimura T, Hirochika R, Iwasaki Y, Inoshita N, Nagano H, Kasai M, Yamamoto H, Yamaguchi T, Suga H, Masaki H. Mizutani, Nakauhi H

    Proceedings of the National Academy of Sciences of the United States of America   Vol. 120 ( 28 ) page: e2216564120   2023.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Patients with permanent hypoparathyroidism require lifelong replacement therapy to avoid life-threatening complications, The benefits of conventional treatment are limited, however. Transplanting a functional parathyroid gland (PTG) would yield better results. Parathyroid gland cells generated from pluripotent stem cells in vitro to date cannot mimic the physiological responses to extracellular calcium that are essential for calcium homeostasis. We thus hypothesized that blastocyst complementation (BC) could be a better strategy for generating functional PTG cells and compensating loss of parathyroid function. We here describe generation of fully functional PTGs from mouse embryonic stem cells (mESCs) with single-step BC. Using CRISPR-Cas9 knockout of Glial cells missing2 (Gcm2), we efficiently produced aparathyroid embryos for BC. In these embryos, mESCs differentiated into endocrinologically mature PTGs that rescued Gcm2-/- mice from neonatal death. The mESC-derived PTGs responded to extracellular calcium, restoring calcium homeostasis on transplantation into mice surgically rendered hypoparathyroid. We also successfully generated functional interspecies PTGs in Gcm2-/- rat neonates, an accomplishment with potential for future human PTG therapy using xenogeneic animal BC. Our results demonstrate that BC can produce functional endocrine organs and constitute a concept in treatment of hypoparathyroidism.

    DOI: 10.1073/pnas.2216564120

    Web of Science

    PubMed

  9. Anti-tumor effects of anti-programmed cell death-1 antibody treatment are attenuated in streptozotocin-induced diabetic mice. Reviewed International journal

    Ito M., Iwama S., Sugiyama D., Yasuda Y., Okuji T., Kobayashi T., Zhou X., Yamagami A., Onoue T., Miyata T., Sugiyama M., Hagiwara D., Suga H., Banno R., Nishikawa H., Arima H.

    Scientific reports   Vol. 13 ( 1 ) page: 5939 - 5939   2023.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Hyperglycemia impairs immune response; however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. We analyzed the effect of PD-1-Ab on tumor growth in streptozotocin-induced diabetic mice (STZ-mice) subcutaneously inoculated with MC38 (a colon carcinoma cell line). Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. The suppressive effect of PD-1-Ab on tumor growth was attenuated. This was accompanied by fewer tumor-infiltrating CD8+ T cells, and STZ-mice had fewer tumor-infiltrating CD11c+ dendritic cells (DCs) than normoglycemic mice. mRNA expression levels of CXCL9, a chemokine recruiting CD8+ T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8+ T cells and decreased expression of CCL7 and CXCL9.

    DOI: 10.1038/s41598-023-33049-7

    Web of Science

    PubMed

  10. Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells. Reviewed International journal

    Miwata T., Suga H., Kawaguchi Y., Sakakibara M., Kano M., Taga S., Soen M., Ozaki H., Asano T., Sasaki H., Miyata T., Yasuda Y., Kobayashi T., Sugiyama M., Onoue T., Takagi H., Hagiwara D., Iwama S., Arima H.

    Stem cell reports   Vol. 18 ( 4 ) page: 869 - 883   2023.4

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    When damaged, restoring the function of the hypothalamus is currently impossible. It is unclear whether neural stem cells exist in the hypothalamus. Studies have reported that adult rodent tanycytes around the third ventricle function as hypothalamic neural stem cell-like cells. However, it is currently impossible to collect periventricular cells from humans. We attempted to generate hypothalamic neural stem cell-like cells from human embryonic stem cells (ESCs). We focused on retina and anterior neural fold homeobox (RAX) because its expression is gradually restricted to tanycytes during the late embryonic stage. We differentiated RAX::VENUS knockin human ESCs (hESCs) into hypothalamic organoids and sorted RAX+ cells from mature organoids. The isolated RAX+ cells formed neurospheres and exhibited self-renewal and multipotency. Neurogenesis was observed when neurospheres were transplanted into the mouse hypothalamus. We isolated RAX+ hypothalamic neural stem cell-like cells from wild-type human ES organoids. This is the first study to differentiate human hypothalamic neural stem cell-like cells from pluripotent stem cells.

    DOI: 10.1016/j.stemcr.2023.02.006

    Web of Science

    PubMed

  11. Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency.

    Kurimoto J, Takagi H, Miyata T, Kawaguchi Y, Hodai Y, Tsumura T, Hagiwara D, Kobayashi T, Yasuda Y, Sugiyama M, Onoue T, Iwama S, Suga H, Banno R, Katsuki T, Ando F, Uchida S, Arima H

    Endocrine journal   Vol. 70 ( 3 ) page: 295 - 304   2023.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1507/endocrj.EJ22-0339

    Web of Science

    PubMed

  12. Subcutaneous transplantation of human embryonic stem cells-derived pituitary organoids Reviewed

    Sasaki H., Suga H., Takeuchi K., Nagata Y., Harada H., Kondo T., Ito E., Maeda S., Sakakibara M., Soen M., Miwata T., Asano T., Ozaki H., Taga S., Kuwahara A., Nakano T., Arima H., Saito R.

    Frontiers in Endocrinology   Vol. 14   page: 1130465 - -   2023.3

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Introduction

    The pituitary gland, regulating various hormones, is central in the endocrine system. As spontaneous recovery from hypopituitarism is rare, and exogenous-hormone substitution is clumsy, pituitary replacement via regenerative medicine, using pluripotent stem cells, is desirable. We have developed a differentiation method that in mice yields pituitary organoids (POs) derived from human embryonic stem cells (hESC). Efficacy of these POs, transplanted subcutaneously into hypopituitary mice, in reversing hypopituitarism was studied.

    Methods

    hESC-derived POs were transplanted into inguinal subcutaneous white adipose tissue (ISWAT) and beneath dorsal skin, a relatively avascular region (AR), of hypophysectomized severe combined immunodeficient (SCID) mice. Pituitary function was evaluated thereafter for ¾ 6mo, assaying basal plasma ACTH and ACTH response to corticotropin-releasing hormone (CRH) stimulation. Histopathologic examination of organoids 150d after transplantation assessed engraftment. Some mice received an inhibitor of vascular endothelial growth factor (VEGF) to permit assessment of how angiogenesis contributed to subcutaneous engraftment.

    Results

    During follow-up, both basal and CRH-stimulated plasma ACTH levels were significantly higher in the ISWAT group (p < 0.001 – 0.05 and 0.001 – 0.005, respectively) than in a sham-operated group. ACTH secretion also was higher in the ISWAT group than in the AR group. Histopathologic study found ACTH-producing human pituitary-cell clusters in both groups of allografts, which had acquired a microvasculature. POs qPCR showed expression of angiogenetic factors. Plasma ACTH levels decreased with VEGF-inhibitor administration.

    Conclusions

    Subcutaneous transplantation of hESC-derived POs into hypopituitary SCID mice efficaciously renders recipients ACTH-sufficient.

    DOI: 10.3389/fendo.2023.1130465

    Web of Science

    PubMed

  13. Resting energy expenditure depends on energy intake during weight loss in people with obesity: a retrospective cohort study. Reviewed International journal

    Handa T., Onoue T., Kobayashi T., Wada E., Hayase A., Kinoshita T., Yamagami A., Yasuda Y., Iwama S., Kawaguchi Y., Miyata T., Sugiyama M., Takagi H., Hagiwara D., Suga H., Banno R., Goto M., Arima H.

    Archives of endocrinology and metabolism   Vol. 67 ( 2 ) page: 233 - 241   2023.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    OBJECTIVE: Resting energy expenditure (REE) decreases if there is reduced energy intake and body weight (BW). The decrease in REE could make it difficult for patients with obesity to maintain decreased BW. This study aimed to investigate the correlation among changes in REE, energy intake, and BW during the weight loss process in patients with obesity. MATERIALS AND METHODS: We conducted a retrospective cohort study of patients hospitalized for the treatment of obesity in Japan. Patients received fully controlled diet during hospitalization and performed exercises if able. REE was measured once a week using a hand-held indirect calorimetry. Energy intake was determined by actual dietary intake. RESULTS: Of 44 inpatients with obesity, 17 were included in the analysis. Their BW decreased significantly after 1 week (-4.7 ± 2.0 kg, P < 0.001) and 2 weeks (-5.7 ± 2.2 kg, P < 0.001). The change in REE after 1 and 2 weeks was positively correlated with the energy intake/energy expenditure ratio (r = 0.66, P = 0.004 at 1 week, r = 0.71, P = 0.002 at 2 weeks). Using a regression equation (y = 0.5257x - 43.579), if the energy intake/energy expenditure ratio within the second week was 82.9%, the REE after 2 weeks was similar to the baseline level. There was no significant correlation between the change in REE and BW. CONCLUSION: Our data suggest that changes in REE depend on energy intake/energy expenditure ratio and that the decrease in REE can be minimized by matching energy intake to energy expenditure, even during the weight loss process.

    DOI: 10.20945/2359-3997000000532

    Web of Science

    PubMed

  14. Recipe for pituitary organoids. International journal

    Kano M, Sasaki H, Miwata T, Suga H

    Frontiers in endocrinology   Vol. 13   page: 1025825 - 1025825   2023.1

     More details

    Authorship:Last author   Language:English   Publishing type:Research paper (scientific journal)  

    Generation of a variety of organs and tissues from human pluripotent stem cells (hPSCs) has been attempted in vitro. We here present a simple and efficient method for induction of hypothalamic and pituitary tissues from hPSCs. On provision of exogenous agents important for early hypothalamus-pituitary organogenesis, including bone morphogenetic protein 4 and activators of sonic hedgehog, in three-dimensional culture, hPSCs spontaneously form spherical organoids with two distinct tissues, hypothalamus and adenohypophysis. The pituitary tissues derived from hPSCs not only secrete adenocorticotropic hormone, but also retain both positive and negative feedback mechanisms, recapitulating mature endocrine organs in vivo. Furthermore, the results of ectopic transplantation with mouse models of hypopituitarism suggest that these hypothalamus-pituitary organoids have potential as engraftment organs. In addition to their use in transplantation for patients with hypopituitarism they will allow establishment of disease models in vitro and enable research impossible in humans. Hypothalamus-pituitary organoids promise to be a powerful tool in regenerative medicine, drug discovery, and basic research into pituitary development.

    DOI: 10.3389/fendo.2022.1025825

    Web of Science

    PubMed

  15. Knockdown of endoplasmic reticulum chaperone BiP leads to the death of parvocellular AVP/CRH neurons in mice

    Kawaguchi, Y; Hagiwara, D; Tsumura, T; Miyata, T; Kobayashi, T; Sugiyama, M; Onoue, T; Yasuda, Y; Iwama, S; Suga, H; Banno, R; Grinevich, V; Arima, H

    JOURNAL OF NEUROENDOCRINOLOGY   Vol. 35 ( 1 ) page: e13223   2023.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/jne.13223

    Web of Science

    PubMed

  16. Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency

    Kurimoto Junki, Takagi Hiroshi, Miyata Takashi, Kawaguchi Yohei, Hodai Yuichi, Tsumura Tetsuro, Hagiwara Daisuke, Kobayashi Tomoko, Yasuda Yoshinori, Sugiyama Mariko, Onoue Takeshi, Iwama Shintaro, Suga Hidetaka, Banno Ryoichi, Katsuki Takeshi, Ando Fumiaki, Uchida Shinichi, Arima Hiroshi

    ENDOCRINE JOURNAL   Vol. 70 ( 3 ) page: 295 - 304   2023

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Web of Science

  17. Long-range axonal projections of transplanted mouse embryonic stem cell-derived hypothalamic neurons into adult mouse brain. International journal

    Kawata M., Kodani Y., Ohkuma M., Miyachi E., Kaneko S.Y., Nakashima A., Suga H., Kameyama T., Saito K., Nagasaki H.

    PloS one   Vol. 17 ( 11 ) page: e0276694   2022.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The hypothalamus is comprised of heterogenous cell populations and includes highly complex neural circuits that regulate the autonomic nerve system. Its dysfunction therefore results in severe endocrine disorders. Although recent experiments have been conducted for in vitro organogenesis of hypothalamic neurons from embryonic stem (ES) or induced pluripotent stem (iPS) cells, whether these stem cell-derived hypothalamic neurons can be useful for regenerative medicine remains unclear. We therefore performed orthotopic transplantation of mouse ES cell (mESC)-derived hypothalamic neurons into adult mouse brains. We generated electrophysiologically functional hypothalamic neurons from mESCs and transplanted them into the supraoptic nucleus of mice. Grafts extended their axons along hypothalamic nerve bundles in host brain, and some of them even projected into the posterior pituitary (PPit), which consists of distal axons of the magnocellular neurons located in hypothalamic supraoptic and paraventricular nuclei. The axonal projections to the PPit were not observed when the mESC-derived hypothalamic neurons were ectopically transplanted into the substantia nigra reticular part. These findings suggest that our stem cell-based orthotopic transplantation approach might contribute to the establishment of regenerative medicine for hypothalamic and pituitary disorders.

    DOI: 10.1371/journal.pone.0276694

    Web of Science

    PubMed

  18. Differentiation of human induced pluripotent stem cells into hypothalamic vasopressin neurons with minimal exogenous signals and partial conversion to the naive state. Reviewed International journal

    Ozaki H, Suga H, Sakakibara M, Soen M, Miyake N, Miwata T, Taga S, Nagai T, Kano, M, Mitsumoto K, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Iwama S, Banno R, Iguchi G, Takahashi Y, Muguruma K, Inoue H, Arima H

    Scientific Reports   Vol. 12 ( 1 ) page: 17381 - -   2022.10

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disease of vasopressin (AVP) neurons. Studies in mouse in vivo models indicate that accumulation of mutant AVP prehormone is associated with FNDI pathology. However, studying human FNDI pathology in vivo is technically challenging. Therefore, an in vitro human model needs to be developed. When exogenous signals are minimized in the early phase of differentiation in vitro, mouse embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) differentiate into AVP neurons, whereas human ESCs/iPSCs die. Human ESCs/iPSCs are generally more similar to mouse epiblast stem cells (mEpiSCs) compared to mouse ESCs. In this study, we converted human FNDI-specific iPSCs by the naive conversion kit. Although the conversion was partial, we found improved cell survival under minimal exogenous signals and differentiation into rostral hypothalamic organoids. Overall, this method provides a simple and straightforward differentiation direction, which may improve the efficiency of hypothalamic differentiation.

    DOI: 10.1038/s41598-022-22405-8

    Web of Science

    PubMed

  19. Elevated TSH level, TgAb and prior use of ramucirumab or TKIs as risk factors for thyroid dysfunction in PD-L1 blockade. Reviewed International journal

    Kobayashi T., Iwama S., Yamagami A., Yasuda Y., Okuji T., Ito M., Zhou X., Ando M., Onoue T., Miyata T., Sugiyama M., Hagiwara D., Suga H., Banno R., Hase T. Morise M., Ito T., Kikumori T., Inoue M., Ando Y., Masuda N., Kawashima H., Hashimoto N., Arima H.

    The Journal of clinical endocrinology and metabolism   Vol. 107 ( 10 ) page: E4115 - E4123   2022.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Thyroid dysfunction is frequently caused by treatment with anti-programmed cell death-1 ligand 1 antibodies (PD-L1-Abs) as well as anti-cancer drugs, including ramucirumab (RAM) and multi-targeted tyrosine kinase inhibitors (multi-TKIs), which are often used prior to PD-L1-Ab treatment in cancer patients. METHODS: A total of 148 patients treated with PD-L1-Abs were evaluated for anti-thyroid antibodies at baseline and for thyroid function every six weeks for 24 weeks after treatment initiation and then were observed until the visits stopped. RESULTS: Of the 148 patients, 15 (10.1%) developed thyroid dysfunction after PD-L1-Ab treatment (destructive thyroiditis in eight and hypothyroidism without preceding thyrotoxicosis in seven). The prevalences of an elevated thyroid-stimulating hormone (TSH) level at baseline (3/15 [20.0%] vs. 4/133 [3.0%], p < 0.05), positive anti-thyroglobulin antibodies (TgAb) at baseline (4/15 [26.7%] vs. 5/133 [3.8%], p < 0.05) and prior treatment with RAM or multi-TKIs (3/15 [20.0%] vs. 5/133 [3.8%], p < 0.05) were significantly higher in patients with versus without thyroid dysfunction. In a multivariate analysis, elevated TSH level at baseline, TgAb positivity at baseline and prior treatment with RAM or multi-TKIs were significantly associated with the development of thyroid dysfunction, with odds ratios of 7.098 (95% confidence interval [CI], 1.154-43.638), 11.927 (95% CI, 2.526-56.316) and 8.476 (95% CI, 1.592-45.115), respectively. CONCLUSIONS: The results of this real-world study suggest that the risk of thyroid dysfunction induced by PD-L1-Abs can be predicted by the TSH level at baseline, TgAb positivity at baseline and prior treatment with RAM or multi-TKIs.

    DOI: 10.1210/clinem/dgac467

    Web of Science

    PubMed

  20. Protein Tyrosine Phosphatase 1B Deficiency Improves Glucose Homeostasis in Insulin-Dependent Diabetes Mellitus Treated with Leptin. Reviewed International journal

    Ito Y., Sun R., Yagimuma H., Taki K., Mizoguchi A., Kobayashi T., Sugiyama M., Onoue T., Tsunekawa T., Takagi H., Hagiwara D., Iwama S., Suga H., Konishi H., Kiyama H., Arima H., Banno R.

    Diabetes   Vol. 71 ( 9 ) page: 1902 - 1914   2022.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Leptin, a hormone secreted by adipocytes, exhibits therapeutic potential for the treatment of insulin-dependent diabetes mellitus (IDDM). Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme that negatively regulates leptin receptor signaling. Here, the role of PTP1B in the treatment of IDDM was investigated using PTP1B deficient (KO) mice and a PTP1B inhibitor. IDDM wild-type (WT) mice induced by streptozotocin showed marked hyperglycemia compared to non-IDDM WT mice. KO mice displayed significantly improved glucose metabolism equivalent to non-IDDM WT mice, whereas peripheral or central administration of leptin partially improved glucose metabolism in IDDM WT mice. Peripheral combination therapy of leptin and a PTP1B inhibitor in IDDM WT mice improved glucose metabolism to the same level as non-IDDM WT mice. Leptin was shown to act on the arcuate nucleus in the hypothalamus to suppress gluconeogenesis in liver and enhance glucose uptake in both brown adipose tissue and soleus muscle via the sympathetic nervous system. These effects were enhanced by PTP1B deficiency. Thus, treatment of IDDM with leptin, PTP1B deficiency or a PTP1B inhibitor was shown to enhance leptin activity in the hypothalamus to improve glucose metabolism. These findings suggest a potential alternative therapy for IDDM.

    DOI: 10.2337/db21-0953

    Web of Science

    PubMed

  21. Inflammation in VTA Caused by HFD Induces Activation of Dopaminergic Neurons Accompanied by Binge-like Eating International journal

    Runan Sun, Mariko Sugiyama, Sixian Wang, Mitsuhiro Kuno, Tomoyuki Sasaki, Tomonori Hirose, Takashi Miyata, Tomoko Kobayashi, Taku Tsunekawa, Takeshi Onoue, Yoshinori Yasuda, Hiroshi Takagi, Daisuke Hagiwara, Shintaro Iwama, Hidetaka Suga, Hiroshi Arima

    Nutrients   Vol. 14 ( 18 ) page: 3835 - 3835   2022.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Binge eating is a characteristic symptom observed in obese individuals that is related to dysfunction of dopaminergic neurons (DNs). Intermittent administration of a high-fat diet (HFD) is reported to induce binge-like eating, but the underlying mechanisms remain unclear. We generated dopaminergic neuron specific IKKβ deficient mice (KO) to examine the effects of inflammation in DNs on binge-like eating under inflammatory conditions associated with HFD. After administration of HFD for 4 weeks, mice were fasted for 24 h, and then the consumption of HFD was measured for 2 h. We also evaluated that the mRNA expressions of inflammatory cytokines, glial markers, and dopamine signaling-related genes in the ventral tegmental area (VTA) and striatum. Moreover, insulin was administered intraventricularly to assess downstream signaling. The consumption of HFD was significantly reduced, and the phosphorylation of AKT in the VTA was significantly increased in female KO compared to wild-type (WT) mice. Analyses of mRNA expressions revealed that DNs activity and inflammation in the VTA were significantly decreased in female KO mice. Thus, our data suggest that HFD-induced inflammation with glial cell activation in the VTA affects DNs function and causes abnormal eating behaviors accompanied by insulin resistance in the VTA of female mice.

    DOI: 10.3390/nu14183835

    Web of Science

    PubMed

  22. Disease Modeling of Pituitary Adenoma Using Human Pluripotent Stem Cells Reviewed

    Matsumoto R., Suga H., Arima H., Yamamoto T.

    Cancers   Vol. 14 ( 15 ) page: 3660   2022.8

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Pituitary adenomas are characterized by abnormal growth in the pituitary gland. Surgical excision is the first-line treatment for functional (hormone-producing) pituitary adenomas, except for prolactin-producing adenomas; however, complete excision is technically challenging, and many patients require long-term medication after the treatment. In addition, the pathophysiology of pituitary adenomas, such as tumorigenesis, has not been fully understood. Pituitary adenoma pathophysiology has mainly been studied using animal models and animal tumor-derived cell lines. Nevertheless, experimental studies on human pituitary adenomas are difficult because of the significant differences among species and the lack of reliable cell lines. Recently, several methods have been established to differentiate pituitary cells from human pluripotent stem cells (hPSCs). The induced pituitary hormone-producing cells retain the physiological properties already lost in tumor-derived cell lines. Moreover, CRISPR/Cas9 systems have expedited the introduction of causative gene mutations in various malignant tumors into hPSCs. Therefore, hPSC-derived pituitary cells have great potential as a novel platform for studying the pathophysiology of human-specific pituitary adenomas and developing novel drugs. This review presents an overview of the recent progresses in hPSC applications for pituitary research, functional pituitary adenoma pathogenesis, and genome-editing techniques for introducing causative mutations. We also discuss future applications of hPSCs for studying pituitary adenomas.

    DOI: 10.3390/cancers14153660

    Web of Science

    Scopus

    PubMed

  23. EpCAM Is a Surface Marker for Enriching Anterior Pituitary Cells From Human Hypothalamic-Pituitary Organoids. Reviewed

    Kodani Y, Kawata M, Suga H, Kasai T, Ozone C, Sakakibara M, Kuwahara A, Taga S, Arima H, Kameyama T, Saito K, Nakashima A, Nagasaki H

    Frontiers in Endocrinology   Vol. 13   page: 941166   2022.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    Human stem cell-derived organoid culture enables the in vitro analysis of the cellular function in three-dimensional aggregates mimicking native organs, and also provides a valuable source of specific cell types in the human body. We previously established organoid models of the hypothalamic-pituitary (HP) complex using human pluripotent stem cells. Although the models are suitable for investigating developmental and functional HP interactions, we consider that isolated pituitary cells are also useful for basic and translational research on the pituitary gland, such as stem cell biology and regenerative medicine. To develop a method for the purification of pituitary cells in HP organoids, we performed surface marker profiling of organoid cells derived from human induced pluripotent stem cells (iPSCs). Screening of 332 human cell surface markers and a subsequent immunohistochemical analysis identified epithelial cell adhesion molecule (EpCAM) as a surface marker of anterior pituitary cells, as well as their ectodermal precursors. EpCAM was not expressed on hypothalamic lineages; thus, anterior pituitary cells were successfully enriched by magnetic separation of EpCAM<sup>+</sup> cells from iPSC-derived HP organoids. The enriched pituitary population contained functional corticotrophs and their progenitors; the former responded normally to a corticotropin-releasing hormone stimulus. Our findings would extend the applicability of organoid culture as a novel source of human anterior pituitary cells, including stem/progenitor cells and their endocrine descendants.

    DOI: 10.3389/fendo.2022.941166

    Web of Science

    PubMed

  24. Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline. International journal

    Iwama S, Kobayashi T, Yasuda Y, Okuji T, Ito M, Ando M, Zhou X, Yamagami A, Onoue T, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Hase T, Morise M, Wakahara K, Yokota K, Kato M, Nishio N, Tanaka C, Miyata K, Ogura A, Ito T, Sawada T, Shimokata T, Niimi K, Ohka F, Ishigami M, Gotoh M, Hashimoto N, Saito R, Kiyoi H, Kajiyama H, Ando Y, Hibi H, Sone M, Akiyama M, Kodera Y, Arima H

    The Journal of clinical endocrinology and metabolism   Vol. 107 ( 4 ) page: E1620 - E1630   2022.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

    DOI: 10.1210/clinem/dgab829

    Web of Science

    PubMed

  25. Functional Lactotrophs in Induced Adenohypophysis Differentiated From Human iPS Cells. Reviewed International journal

    Miyake N, Nagai T, Suga H, Osuka S, Kasai T, Sakakibara M, Soen M, Ozaki H, Miwata T, Asano T, Kano M, Muraoka A, Nakanishi N, Nakamura T, Goto M, Yasuda Y, Kawaguchi Y, Miyata T, Kobayashi T, Sugiyama M, Onoue T, Hagiwara D, Iwama S, Iwase A, Inoshita N, Arima H, Kajiyama H

    Endocrinology   Vol. 163 ( 3 ) page: bqac004 - -   2022.3

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Prolactin (PRL), a hormone involved in lactation, is mainly produced and secreted by the lactotrophs of the anterior pituitary (AP) gland. We previously reported a method to generate functional adrenocorticotropic hormone-producing cells by differentiating the AP and hypothalamus simultaneously from human induced pluripotent stem cells (iPSCs). However, PRL-producing cells in the induced AP have not been investigated. Here, we confirmed the presence of PRL-producing cells and evaluated their endocrine functions. We differentiated pituitary cells from human iPSCs using serum-free floating culture of embryoid-like aggregates with quick reaggregation (SFEB-q) method and evaluated the appearance and function of PRL-producing cells. Secretion of PRL from the differentiated aggregates was confirmed, which increased with further culture. Fluorescence immunostaining and immunoelectron microscopy revealed PRL-producing cells and PRL-positive secretory granules, respectively. PRL secretion was promoted by various prolactin secretagogues such as thyrotropin-releasing hormone, vasoactive intestinal peptide, and prolactin-releasing peptide, and inhibited by bromocriptine. Moreover, the presence of tyrosine hydroxylase-positive dopaminergic nerves in the hypothalamic tissue area around the center of the aggregates connecting to PRL-producing cells indicated the possibility of recapitulating PRL regulatory mechanisms through the hypothalamus. In conclusion, we generated pituitary lactotrophs from human iPSCs; these displayed similar secretory responsiveness as human pituitary cells in vivo. In the future, this is expected to be used as a model of human PRL-producing cells for various studies, such as drug discovery, prediction of side effects, and elucidation of tumorigenic mechanisms using disease-specific iPSCs. Furthermore, it may help to develop regenerative medicine for the pituitary gland.

    DOI: 10.1210/endocr/bqac004

    Web of Science

    PubMed

  26. Characterization of Hypothalamic MCH Neuron Development in a 3D Differentiation System of Mouse Embryonic Stem Cells Reviewed International journal

    Kodani Y., Kawata M., Suga H., Kaneko S. Y., Nakashima A., Kameyama T., Saito K., Nagasaki H.

    eneuro   Vol. 9 ( 2 ) page: ENEURO.0442 - 21.2022   2022.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Society for Neuroscience  

    Hypothalamic melanin-concentrating hormone (MCH) neurons are important regulators of multiple physiological processes, such as sleep, feeding, and memory. Despite the increasing interest in their neuronal functions, the molecular mechanism underlying MCH neuron development remains poorly understood. We report that a three-dimensional culture of mouse embryonic stem cells (mESCs) can generate hypothalamic-like tissues containing MCH-positive neurons, which reproduce morphologic maturation, neuronal connectivity, and neuropeptide/neurotransmitter phenotype of native MCH neurons. Using this in vitro system, we demonstrate that Hedgehog (Hh) signaling serves to produce major neurochemical subtypes of MCH neurons characterized by the presence or absence of cocaine- and amphetamine-regulated transcript (CART). Without exogenous Hh signals, mESCs initially differentiated into dorsal hypothalamic/prethalamic progenitors and finally into MCH+CART+ neurons through a specific intermediate progenitor state. Conversely, activation of the Hh pathway specified ventral hypothalamic progenitors that generate both MCH+CART- and MCH+CART+ neurons. These results suggest that in vivo MCH neurons may originate from multiple cell lineages that arise through early dorsoventral patterning of the hypothalamus. Additionally, we found that Hh signaling supports the differentiation of mESCs into orexin/hypocretin neurons, a well-defined cell group intermingled with MCH neurons in the lateral hypothalamic area (LHA). The present study highlights and improves the utility of mESC culture in the analysis of the developmental programs of specific hypothalamic cell types.Significance StatementA growing body of literature has revealed the importance of hypothalamic melanin-concentrating hormone (MCH) neurons in energy homeostasis and the cognitive function, but their developmental biology remains relatively unknown. To establish a new approach for addressing this issue, we tested the ability of an in vitro differentiation system of mouse embryonic stem cells (mESCs) to recapitulate the development of MCH neurons. The mESC culture robustly generated MCH-positive neurons resembling native neurons in several aspects and provided evidence that Hedgehog (Hh) signaling is a key factor to produce neurochemical subtypes of MCH neurons. Our results demonstrate the suitability of mESC culture as a platform to study the molecular mechanisms underlying the development of MCH neurons and possibly of other hypothalamic cell types.

    DOI: 10.1523/ENEURO.0442-21.2022

    Web of Science

    PubMed

  27. ヒト疾患特異的人工多能性幹細胞(iPS細胞)からのバソプレシン(AVP)神経の分化誘導による家族性中枢性尿崩症(FNDI)のin vitroヒト疾患モデル

    尾崎 創, 須賀 英隆, 三輪田 勤, 井口 元三, 高橋 裕, 有馬 寛

    日本内分泌学会雑誌   Vol. 97 ( 5 ) page: 1243 - 1243   2022.3

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本内分泌学会  

  28. Predicting non-insulin-dependent state in patients with slowly progressive insulin-dependent (type 1) diabetes mellitus or latent autoimmune diabetes in adults. Reply to Sugiyama K and Saisho Y [letter]

    Wada, E; Onoue, T; Kinoshita, T; Hayase, A; Handa, T; Ito, M; Furukawa, M; Okuji, T; Kobayashi, T; Iwama, S; Sugiyama, M; Takagi, H; Hagiwara, D; Suga, H; Banno, R; Goto, M; Arima, H

    DIABETOLOGIA   Vol. 65 ( 1 ) page: 252 - 253   2022.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00125-021-05610-4

    Web of Science

    PubMed

  29. Adult-onset autoimmune diabetes identified by glutamic acid decarboxylase autoantibodies: a retrospective cohort study

    Wada, E; Onoue, T; Kinoshita, T; Hayase, A; Handa, T; Ito, M; Furukawa, M; Okuji, T; Kobayashi, T; Iwama, S; Sugiyama, M; Takagi, H; Hagiwara, D; Suga, H; Banno, R; Goto, M; Arima, H

    DIABETOLOGIA   Vol. 64 ( 10 ) page: 2183 - 2192   2021.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00125-021-05516-1

    Web of Science

    PubMed

  30. GABAB receptor signaling in the caudate putamen is involved in binge-like consumption during a high fat diet in mice. International journal

    Sun R., Tsunekawa T., Hirose T., Yaginuma H., Taki K., Mizoguchi A., Miyata T., Kobayashi T., Sugiyama M., Onoue T., Takagi H., Hagiwara D., Ito Y., Iwama S., Suga H., Banno R., Bettler B., Arima H.

    Scientific reports   Vol. 11 ( 1 ) page: 19296 - 19296   2021.9

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Previous studies suggest that signaling by the gamma-aminobutyric acid (GABA) type B receptor (GABABR) is involved in the regulation of binge eating, a disorder which might contribute to the development of obesity. Here, we show that intermittent access to a high fat diet (HFD) induced binge-like eating behavior with activation of dopamine receptor d1 (drd1)-expressing neurons in the caudate putamen (CPu) and nucleus accumbens (NAc) in wild-type (WT) mice. The activation of drd1-expressing neurons during binge-like eating was substantially increased in the CPu, but not in the NAc, in corticostriatal neuron-specific GABABR-deficient knockout (KO) mice compared to WT mice. Treatment with the GABABR agonist, baclofen, suppressed binge-like eating behavior in WT mice, but not in KO mice, as reported previously. Baclofen also suppressed the activation of drd1-expressing neurons in the CPu, but not in the NAc, during binge-like eating in WT mice. Thus, our data suggest that GABABR signaling in CPu neurons expressing drd1 suppresses binge-like consumption during a HFD in mice.

    DOI: 10.1038/s41598-021-98590-9

    Web of Science

    PubMed

  31. Deficiency of WFS1 leads to the impairment of AVP secretion under dehydration in male mice Reviewed International journal

    Kurimoto J., Takagi H., Miyata T., Hodai Y., Kawaguchi Y., Hagiwara D., Suga H., Kobayashi T., Sugiyama M., Onoue T., Ito Y., Iwama S., Banno R., Tanabe K., Tanizawa Y., Arima H.

    Pituitary   Vol. 24 ( 4 ) page: 582 - 588   2021.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    Wolfram syndrome (WS) is mainly caused by mutations in the WFS1 gene and characterized by diabetes mellitus, optic atrophy, hearing loss, and central diabetes insipidus (CDI). WFS1 is an endoplasmic reticulum (ER)-resident transmembrane protein, and Wfs1 knockout (Wfs1-/-) mice, which have been used as a mouse model for WS, reportedly manifested impairment of glucose tolerance due to pancreatic β-cell loss. In the present study, we examined water balance, arginine vasopressin (AVP) secretion, and ER stress in AVP neurons of the hypothalamus in Wfs1-/- mice. There were no differences in urine volumes between Wfs1-/- and wild-type mice with free access to water. Conversely, when mice were subjected to intermittent water deprivation (WD) for 20 weeks, during which water was unavailable for 2 days a week, urine volumes were larger in Wfs1-/- mice, accompanied by lower urine AVP concentrations and urine osmolality, compared to wild-type mice. The mRNA expression of immunoglobulin heavy chain binding protein, a marker of ER stress, was significantly increased in the supraoptic nucleus and paraventricular nuclei in Wfs1-/- mice compared to wild-type mice after WD. Our results thus showed that Wfs1 knockout leads to a decrease in AVP secretion during dehydration, which could explain in part the mechanisms by which Wfs1 mutations cause CDI in humans.

    DOI: 10.1007/s11102-021-01135-6

    Web of Science

    PubMed

    Other Link: http://link.springer.com/article/10.1007/s11102-021-01135-6/fulltext.html

  32. Adult-onset autoimmune diabetes identified by glutamic acid decarboxylase autoantibodies: a retrospective cohort study. Reviewed

    Wada E, Onoue T, Kinoshita T, Hayase A, Handa T, Ito M, Furukawa M, Okuji T, Kobayashi T, Iwama S, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Goto M, Arima H

    DIABETOLOGIA   Vol. 64 ( 10 ) page: 2183 - 2192   2021.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  33. Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice Invited

    Mizoguchi Akira, Banno Ryoichi, Sun Runan, Yaginuma Hiroshi, Taki Keigo, Kobayashi Tomoko, Sugiyama Mariko, Tsunekawa Taku, Onoue Takeshi, Takagi Hiroshi, Hagiwara Daisuke, Ito Yoshihiro, Iwama Shintaro, Suga Hidetaka, Nagai Taku, Yamada Kiyofumi, Arima Hiroshi

    SCIENTIFIC REPORTS   Vol. 11 ( 1 ) page: 12873   2021.6

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-021-92386-7

    Web of Science

    PubMed

  34. Glucocorticoid receptor signaling in ventral tegmental area neurons increases the rewarding value of a high-fat diet in mice. Reviewed

    Mizoguchi, A, Banno, R, Sun, R, Yaginuma, H, Taki, K, Kobayashi, T, Sugiyama, M, Tsunekawa, T, Onoue, T, Takagi, H, Hagiwara, D, Ito, Y, Iwama, S, Suga, H, Nagai, T, Yamada, K, Arima, H

    Scientific Reports   Vol. 11   page: 12873 - -   2021.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  35. A new primate model of hypophyseal dysfunction Reviewed International journal

    Kawabata T, Suga H, Takeuchi K, Nagata Y, Sakakibara M, Ushida K, Ozone C, Enomoto A, Kawamoto I, Itagaki I, Tsuchiya H, Arima H, Wakabayashi T

    Scientific Reports   Vol. 11 ( 1 ) page: 10729 - 10729   2021.5

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

    DOI: 10.1038/s41598-021-90209-3

    Web of Science

    PubMed

    Other Link: http://www.nature.com/articles/s41598-021-90209-3

  36. CD4(+) T cells are essential for the development of destructive thyroiditis induced by anti-PD-1 antibody in thyroglobulin-immunized mice

    Yasuda Yoshinori, Iwama Shintaro, Sugiyama Daisuke, Okuji Takayuki, Kobayashi Tomoko, Ito Masaaki, Okada Norio, Enomoto Atsushi, Ito Sachiko, Yan Yue, Sugiyama Mariko, Onoue Takeshi, Tsunekawa Taku, Ito Yoshihiro, Takagi Hiroshi, Hagiwara Daisuke, Goto Motomitsu, Suga Hidetaka, Banno Ryoichi, Takahashi Masahide, Nishikawa Hiroyoshi, Arima Hiroshi

    SCIENCE TRANSLATIONAL MEDICINE   Vol. 13 ( 593 )   2021.5

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

    DOI: 10.1126/scitranslmed.abb7495

    Web of Science

    PubMed

  37. High-fat Feeding Causes Inflammation and Insulin Resistance in the Ventral Tegmental Area in Mice. Reviewed International journal

    Mizoguchi A., Banno R., Sun R., Yaginuma H., Taki K., Kobayashi T. Sugiyama M., Tsunekawa T., Onoue T., Takagi H., Hagiwara D., Ito Y., Iwama S., Suga H., Arima H.

    Neuroscience   Vol. 461   page: 72 - 79   2021.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The reward system plays an important role in the pathogenesis of not only drug addiction, but also diet-induced obesity. Recent studies have shown that insulin and leptin receptor signaling in the ventral tegmental area (VTA) regulate energy homeostasis and that their dysregulation is responsible for obesity and altered food preferences. Although a high-fat diet (HFD) induces inflammation that leads to insulin and leptin resistance in the brain, it remains unclear whether HFD induces inflammation in the VTA. In the present study, we placed male mice on a chow diet or HFD for 3, 7, and 28 days and evaluated the mRNA expression of inflammatory cytokines and microglial activation markers in the VTA. The HFD group showed significantly elevated mRNA expressions of IL1β at 3 days; tumor necrosis factor-alpha (TNFα), IL1β, IL6, Iba1, and CD11b at 7 days; and TNFα, IL1β, Iba1, and CD11b at 28 days. The changes in TNFα were also confirmed in immunohistochemical analysis. Next, after administration of chow or HFD for 7 days, we selected mice with equal weights in both groups. In experiments using these mice, Akt phosphorylation in the VTA was significantly decreased after intracerebroventricular injection of insulin, whereas no change in STAT3 phosphorylation was found with leptin. Taken together, these results suggest that HFD induces inflammation at least partly associated with microglial activation in the VTA leading to insulin resistance, independently of the energy balance. Our data provide new insight into the pathophysiology of obesity caused by a dysfunctional reward system under HFD conditions.

    DOI: 10.1016/j.neuroscience.2021.02.009

    Web of Science

    PubMed

  38. Arginine vasopressin-Venus reporter mice as a tool for studying magnocellular arginine vasopressin neurons. Reviewed International journal

    Hagiwara D., Tochiya M., Azuma Y., Tsumura T., Hodai Y., Kawaguchi Y., Miyata T., Kobayashi T., Sugiyama M., Onoue T., Takagi H., Ito Y., Iwama S., Suga H., Banno R., Arima H.

    Peptides   Vol. 139   page: 170517 - 170517   2021.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Arginine vasopressin (AVP) synthesized in the magnocellular neurons of the hypothalamus is transported through their axons and released from the posterior pituitary into the systemic circulation to act as an antidiuretic hormone. AVP synthesis and release are precisely regulated by changes in plasma osmolality. Magnocellular AVP neurons receive innervation from osmosensory and sodium-sensing neurons, but previous studies showed that AVP neurons per se are osmosensitive as well. In the current study, we made AVP-Venus reporter mice and showed that Venus was expressed exclusively in AVP neurons and was upregulated under water deprivation. In hypothalamic organotypic cultures from the AVP-Venus mice, Venus-labeled AVP neurons in the supraoptic and paraventricular nuclei survived for 1 month, and Venus expression was upregulated by forskolin. Furthermore, in dissociated Venus-labeled magnocellular neurons, treatment with NaCl, but not with mannitol, decreased Venus fluorescence in the soma of the AVP neurons. Thus, Venus expression in AVP-Venus transgenic mice, as well as in primary cultures, faithfully showed the properties of intrinsic AVP expression. These findings indicate that AVP-Venus mice as well as the primary hypothalamic cultures could be useful for studying magnocellular AVP neurons.

    DOI: 10.1016/j.peptides.2021.170517

    Web of Science

    PubMed

  39. Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors Reviewed International journal

    Kobayashi T., Iwama S., Sugiyama D., Yasuda Y., Okuji T., Ito M., Ito S., Sugiyama M., Onoue T., Takagi H., Hagiwara D., Ito Y., Suga H., Banno R., Nishikawa H., Arima H.

    Journal for ImmunoTherapy of Cancer   Vol. 9 ( 5 ) page: e002493 - e002493   2021.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMJ  

    Background

    Pituitary dysfunction is a life-threatening immune-related adverse event (irAE) induced by immune checkpoint inhibitors (ICIs). To date, it is not possible to identify patients who may develop pituitary irAEs prior to ICI treatment. The aim of this study was to characterize the predisposition for ICI-induced pituitary irAEs by analyzing anti-pituitary antibodies (APAs) and human leukocyte antigens (HLAs).

    Methods

    In this case–control study, APAs and HLA alleles were analyzed in 62 patients (17 who developed ICI-induced isolated adrenocorticotropic hormone deficiency (ICI-IAD), 5 who developed ICI-induced hypophysitis (ICI-H) and 40 who did not develop pituitary irAEs) treated with ICIs between November 2, 2015, and March 31, 2020, at Nagoya University Hospital. The main outcome measures in this study were the association between the development of pituitary irAEs with APAs at baseline and after treatment and HLA alleles.

    Results

    Eleven of 17 (64.7%) patients who developed ICI-IAD had APAs at baseline, whereas APAs were positive only in 1 of 40 (2.5%) control patients. Although APAs were negative at baseline in all patients who developed ICI-H, they had become positive before the onset of ICI-H in 3 of 4 patients several weeks after ipilimumab administration. At the onset of ICI-IAD and ICI-H, APAs were positive in 15 of 17 (88.2%) and 4 of 5 (80%) patients, respectively. The prevalence of HLA-Cw12, HLA-DR15, HLA-DQ7, and HLA-DPw9 was significantly higher in patients with ICI-IAD, whereas that of HLA-Cw12 and HLA-DR15 was significantly higher in patients with ICI-H than in controls.

    Conclusions

    This study showed distinct and overlapped patterns of APAs and HLA alleles between ICI-IAD and ICI-H. Our findings also showed that positive APAs at baseline and after treatment, together with susceptible HLA alleles, could become predictive biomarkers for ICI-IAD and ICI-H, respectively.

    Trial registration number

    UMIN000019024.

    DOI: 10.1136/jitc-2021-002493

    Web of Science

    PubMed

  40. Dietary sodium chloride attenuates increased β-cell mass to cause glucose intolerance in mice under a high-fat diet. Reviewed International journal

    Taki K, Takagi H, Hirose T, Sun R, Yaginuma H, Mizoguchi A, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Hagiwara D, Ito Y, Iwama S, Suga H, Banno R, Sakano D, Kume S, Arima H

    PloS one   Vol. 16 ( 3 ) page: e0248065   2021.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Excessive sodium salt (NaCl) or fat intake is associated with a variety of increased health risks. However, whether excessive NaCl intake accompanied by a high-fat diet (HFD) affects glucose metabolism has not been elucidated. In this study, C57BL/6J male mice were fed a normal chow diet (NCD), a NCD plus high-NaCl diet (NCD plus NaCl), a HFD, or a HFD plus high-NaCl diet (HFD plus NaCl) for 30 weeks. No significant differences in body weight gain, insulin sensitivity, and glucose tolerance were observed between NCD-fed and NCD plus NaCl-fed mice. In contrast, body and liver weights were decreased, but the weight of epididymal white adipose tissue was increased in HFD plus NaCl-fed compared to HFD-fed mice. HFD plus NaCl-fed mice had lower plasma glucose levels in an insulin tolerance test, and showed higher plasma glucose and lower plasma insulin levels in an intraperitoneal glucose tolerance test compared to HFD-fed mice. The β-cell area and number of islets were decreased in HFD plus NaCl-fed compared to HFD-fed mice. Increased Ki67-positive β-cells, and increased expression levels of Ki67, CyclinB1, and CyclinD1 mRNA in islets were observed in HFD-fed but not HFD plus NaCl-fed mice when compared to NCD-fed mice. Our data suggest that excessive NaCl intake accompanied by a HFD exacerbates glucose intolerance, with impairment in insulin secretion caused by the attenuation of expansion of β-cell mass in the pancreas.

    DOI: 10.1371/journal.pone.0248065

    Web of Science

    PubMed

  41. Induction of Functional Hypothalamus and Pituitary Tissues From Pluripotent Stem Cells for Regenerative Medicine. Reviewed International journal

    Kano M., Suga H., Arima H.

    Journal of the Endocrine Society   Vol. 5 ( 3 ) page: bvaa188   2021.3

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    The hypothalamus and pituitary have been identified to play essential roles in maintaining homeostasis. Various diseases can disrupt the functions of these systems, which can often result in serious lifelong symptoms. The current treatment for hypopituitarism involves hormone replacement therapy. However, exogenous drug administration cannot mimic the physiological changes that are a result of hormone requirements. Therefore, patients are at a high risk of severe hormone deficiency, including adrenal crisis. Pluripotent stem cells (PSCs) self-proliferate and differentiate into all types of cells. The generation of endocrine tissues from PSCs has been considered as another new treatment for hypopituitarism. Our colleagues established a 3-dimensional (3D) culture method for embryonic stem cells (ESCs). In this culture, the ESC-derived aggregates exhibit self-organization and spontaneous formation of highly ordered patterning. Recent results have shown that strict removal of exogenous patterning factors during early differentiation efficiently induces rostral hypothalamic progenitors from mouse ESCs. These hypothalamic progenitors generate vasopressinergic neurons, which release neuropeptides upon exogenous stimulation. Subsequently, we reported adenohypophysis tissue self-formation in 3D cultures of mouse ESCs. The ESCs were found to differentiate into both nonneural oral ectoderm and hypothalamic neuroectoderm in adjacent layers. Interactions between the 2 tissues appear to be critically important for in vitro induction of a Rathke's pouch-like developing embryo. Various endocrine cells were differentiated from nonneural ectoderm. The induced corticotrophs efficiently secreted adrenocorticotropic hormone when engrafted in vivo, which rescued hypopituitary hosts. For future regenerative medicine, generation of hypothalamic and pituitary tissues from human PSCs is necessary. We and other groups succeeded in establishing a differentiation method with the use of human PSCs. Researchers could use these methods for models of human diseases to elucidate disease pathology or screen potential therapeutics.

    DOI: 10.1210/jendso/bvaa188

    Web of Science

    PubMed

  42. Hypothalamic-pituitary organoid generation through the recapitulation of organogenesis. Reviewed

    Ozaki H, Suga H, Arima H

    Development, growth & differentiation   Vol. 63 ( 2 ) page: 154 - 165   2021.2

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    This paper overviews the development and differentiation of the hypothalamus and pituitary gland from embryonic stem (ES) and induced pluripotent stem (iPS) cells. It is important to replicate the developmental process in vivo to create specific cells/organoids from ES/iPS cells. We also introduce the latest findings and discuss future issues for clinical application. Neuroectodermal progenitors are induced from pluripotent stem cells by strictly removing exogenous patterning factors during the early differentiation period. The induced progenitors differentiate into rostral hypothalamic neurons, in particular magnocellular vasopressin+ neurons. In three-dimensional cultures, the ES/iPS cells differentiate into hypothalamic neuroectoderm as well as non-neural head ectoderm back to back. Rathke's pouch-like structures self-organize at the interface between the two layers and generated various endocrine cells, including corticotrophs and somatotrophs from the Rathke's pouch-like structures. Our next objective is to sophisticate our stepwise methodology to establish the novel transplantation treatment for hypopituitarism and to apply it to developmental disease models.

    DOI: 10.1111/dgd.12719

    Web of Science

    PubMed

  43. Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice

    Yaginuma H, Banno R, Sun R, Taki K, Mizoguchi A, Kobayashi T, Sugiyama M, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Suga H, Arima H

    JOURNAL OF PHARMACOLOGICAL SCIENCES   Vol. 147 ( 4 ) page: 340 - 347   2021

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPANESE PHARMACOLOGICAL SOC  

    We investigated whether peripheral combination treatment of a sodium-glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 mu g/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin. (C) 2021 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

    DOI: 10.1016/j.jphs.2021.08.010

    Web of Science

    PubMed

  44. Endoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice Reviewed International journal

    Yohei Kawaguchi, Daisuke Hagiwara, Takashi Miyata, Yuichi Hodai, Junki Kurimoto, Hiroshi Takagi, Hidetaka Suga, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Yoshihiro Ito, Shintaro Iwama, Ryoichi Banno, Valery Grinevich, Hiroshi Arima

    Scientific Reports   Vol. 10 ( 1 ) page: 19730 - 19730   2020.11

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>The immunoglobulin heavy chain binding protein (BiP), also referred to as 78-kDa glucose-regulated protein (GRP78), is a pivotal endoplasmic reticulum (ER) chaperone which modulates the unfolded protein response under ER stress. Our previous studies showed that BiP is expressed in arginine vasopressin (AVP) neurons under non-stress conditions and that BiP expression is upregulated in proportion to the increased AVP expression under dehydration. To clarify the role of BiP in AVP neurons, we used a viral approach in combination with shRNA interference for BiP knockdown in mouse AVP neurons. Injection of a recombinant adeno-associated virus equipped with a mouse AVP promoter and BiP shRNA cassette provided specific BiP knockdown in AVP neurons of the supraoptic (SON) and paraventricular nuclei (PVN) in mice. AVP neuron-specific BiP knockdown led to ER stress and AVP neuronal loss in the SON and PVN, resulting in increased urine volume due to lack of AVP secretion. Immunoelectron microscopy of AVP neurons revealed that autophagy was activated through the process of AVP neuronal loss, whereas no obvious features characteristic of apoptosis were observed. Pharmacological inhibition of autophagy by chloroquine exacerbated the AVP neuronal loss due to BiP knockdown, indicating a protective role of autophagy in AVP neurons under ER stress. In summary, our results demonstrate that BiP is essential for the AVP neuron system.

    DOI: 10.1038/s41598-020-76839-z

    Web of Science

    PubMed

    Other Link: http://www.nature.com/articles/s41598-020-76839-z

  45. Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons. International journal

    Takashi Miyata, Daisuke Hagiwara, Yuichi Hodai, Tsutomu Miwata, Yohei Kawaguchi, Junki Kurimoto, Hajime Ozaki, Kazuki Mitsumoto, Hiroshi Takagi, Hidetaka Suga, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Yoshihiro Ito, Shintaro Iwama, Ryoichi Banno, Mami Matsumoto, Natsuko Kawakami, Nobuhiko Ohno, Hirotaka Sakamoto, Hiroshi Arima

    iScience   Vol. 23 ( 10 ) page: 101648 - 101648   2020.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER.

    DOI: 10.1016/j.isci.2020.101648

    Web of Science

    PubMed

  46. Generation of four induced pluripotent stem cell lines (FHUi003-A, FHUi003-B, FHUi004-A and FHUi004-B) from two affected individuals of a familial neurohypophyseal diabetes insipidus family Reviewed International journal

    Satoru Yoshida, Hanayuki Okura, Hidetaka Suga, Mika Soen, Yohei Kawaguchi, Junki Kurimoto, Takashi Miyata, Hiroshi Takagi, Hiroshi Arima, Tatsuya Fujikawa, Fumio Otsuka, Akifumi Matsuyama

    Stem Cell Research   Vol. 48   page: 101960 - 101960   2020.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    Four disease-specific induced pluripotent stem cell (iPSC) lines were respectively derived from peripheral blood mononuclear cells of two affected individuals in a family affected by familial neurohypophyseal diabetes insipidus carrying the c.314G>C mutation. The expression of pluripotency markers (NANOG, OCT4, and SOX2), maintenance of a normal karyotype, absence of episomal vectors used for iPSC generation, and presence of the original pathogenic mutation were confirmed for each iPSC line. The ability to differentiate into three germ layers was confirmed by a teratoma formation assay. These iPSC lines can help in disease recapitulation in vitro using organoids and elucidation of disease mechanisms.

    DOI: 10.1016/j.scr.2020.101960

    Web of Science

    PubMed

  47. Generation of three induced pluripotent stem cell (iPSC) lines from a multiple endocrine neoplasia type 1 (MEN1) patient and three iPSC lines from an unaffected relative of the patient. Reviewed International journal

    Satoru Yoshida, Hanayuki Okura, Hidetaka Suga, Tomohiko Nishitomi, Akihiro Sakurai, Hiroshi Arima, Akifumi Matsuyama

    Stem cell research   Vol. 46   page: 101846 - 101846   2020.7

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    We generated three disease-specific iPSC lines from a Multiple endocrine neoplasia type 1 (MEN1) patient and three control iPSC lines from an unaffected blood relative of the patient using unutilized lymphoblastoid B cell lines (LCLs) as a cell resource. The expression of pluripotency markers, retaining of normal karyotype of chromosome, absence of episomal vectors used for generating the iPSCs and EBV used for generating LCLs, and the potential to differentiate into three germ layers, were confirmed for each iPSC line. These iPSC lines can be useful for construction of the disease models in vitro, and elucidation of the disease mechanisms.

    DOI: 10.1016/j.scr.2020.101846

    Web of Science

    PubMed

  48. Hypothalamic glial cells isolated by MACS reveal that microglia and astrocytes induce hypothalamic inflammation via different processes under high-fat diet conditions Reviewed International journal

    Mariko Sugiyama, Ryoichi Banno, Hiroshi Yaginuma, Keigo Taki, Akira Mizoguchi, Taku Tsunekawa, Takeshi Onoue, Hiroshi Takagi, Yoshihiro Ito, Shintaro Iwama, Motomitsu Goto, Hidetaka Suga, Okiru Komine, Koji Yamanaka, Hiroshi Arima

    Neurochemistry International   Vol. 136   page: 104733 - 104733   2020.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    Glial cells can mediate hypothalamic inflammatory processes induced in response to a high-fat diet (HFD). We used magnetic-activated cell sorting (MACS) to isolate microglia and astrocytes from hypothalamus of mice fed HFD and examined changes in expression of inflammation-related cytokines and markers related to glial cell activation status. Hypothalamus from male C57BL6 mice fed a chow diet (chow) or HFD for 1, 3, or 28 days were collected and microglia and astrocytes were isolated by MACS. After confirming cell viability by fluorescence activated cell sorting, mRNA expression levels of inflammation-related cytokines and markers of glial cell activation status were examined by qRT-PCR, which revealed that both glial cell types isolated by MACS retained specificity. On day 3 of HFD, both CD86 and TNFα mRNA expression was significantly increased in microglia relative to the chow group. In astrocytes, TNFα mRNA expression levels were similar between the chow and HFD groups on day 3, but anti-inflammatory cytokine IL-10 levels were significantly increased. On day 7 of HFD, TNFα expression in microglia decreased to levels comparable to the chow group while that in astrocytes remained unchanged. On day 28 of HFD, TNFα levels were significantly increased in both microglia and astrocytes, which had increased mRNA expression of CD86 and MAO-B, respectively. For both glial cell types, results for TNFα expression assessed by RT-PCR and immunohistochemical analysis were similar. These results indicate that the role of microglia and astrocytes in hypothalamic inflammation under HFD conditions changed with time and these changes were accompanied by changes in the activation status of glial cells. Our data suggest that early after initiating HFD, hypothalamic astrocytes suppress diet-induced inflammation at least in part by secreting IL-10, whereas continued HFD feeding impairs this suppressive function such that both microglia and astrocytes promote hypothalamic inflammation.

    DOI: 10.1016/j.neuint.2020.104733

    Web of Science

    PubMed

  49. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Reviewed International journal

    Norio Okada, Shintaro Iwama, Takayuki Okuji, Tomoko Kobayashi, Yoshinori Yasuda, Eri Wada, Takeshi Onoue, Motomitsu Goto, Mariko Sugiyama, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Mitsuro Kanda, Kenji Yokota, Naozumi Hashimoto, Masahiko Ando, Yasushi Fujimoto, Masato Nagino, Yasuhiro Kodera, Mitsuhiro Fujishiro, Hideharu Hibi, Michihiko Sone, Hitoshi Kiyoi, Momokazu Gotoh, Yuichi Ando, Masashi Akiyama, Yoshinori Hasegawa, Hiroshi Arima

    British journal of cancer   Vol. 122 ( 6 ) page: 771 - 777   2020.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    BACKGROUND: Anti-programmed cell death-1 (PD-1) antibodies can cause thyroid dysfunction. However, no predictive biomarkers enabling stratification of thyroid dysfunction risk have been identified. METHODS: A total of 209 patients treated with an anti-PD-1 antibody were evaluated for anti-thyroid antibodies at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the visits stopped. Thyroid ultrasonography was performed if the patient was positive for anti-thyroid antibodies at baseline. RESULTS: Of the 209 patients, 19 (9.1%) developed thyroid dysfunction (destructive thyroiditis or hypothyroidism). The cumulative incidence of thyroid dysfunction was significantly higher in patients who were positive vs. negative for anti-thyroid antibodies (15/44 [34.1%] vs. 4/165 [2.4%], p < 0.001). Forty-two patients positive for anti-thyroid antibodies at baseline were divided into two groups according to the presence of an irregular echo pattern. The cumulative incidence of thyroid dysfunction was significantly higher in those with an irregular vs. a regular echo pattern (13/23 [56.5%] vs. 1/19 [5.3%], p = 0.001). None of the patients developed thyroid dysfunction after the initial 24-week period. CONCLUSIONS: The risk of thyroid dysfunction induced by anti-PD-1 antibodies can be predicted by evaluation of anti-thyroid antibodies and the thyroid echo pattern at baseline. TRIAL REGISTRATION: UMIN000019024.

    DOI: 10.1038/s41416-020-0736-7

    Web of Science

    PubMed

    Other Link: http://www.nature.com/articles/s41416-020-0736-7

  50. Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells. Reviewed International journal

    Ryusaku Matsumoto, Hidetaka Suga, Takashi Aoi, Hironori Bando, Hidenori Fukuoka, Genzo Iguchi, Satoshi Narumi, Tomonobu Hasegawa, Keiko Muguruma, Wataru Ogawa, Yutaka Takahashi

    The Journal of clinical investigation   Vol. 130 ( 2 ) page: 641 - 654   2020.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Pituitary develops from oral ectoderm in contact with adjacent ventral hypothalamus. Impairment in this process results in congenital pituitary hypoplasia (CPH); however, there have been no human disease models for CPH thus far, prohibiting the elucidation of the underlying mechanisms. In this study, we established a disease model of CPH using patient-derived induced pluripotent stem cells (iPSCs) and 3D organoid technique, in which oral ectoderm and hypothalamus develop simultaneously. Interestingly, patient iPSCs with a heterozygous mutation in the orthodenticle homeobox 2 (OTX2) gene showed increased apoptosis in the pituitary progenitor cells, and the differentiation into pituitary hormone-producing cells was severely impaired. As an underlying mechanism, OTX2 in hypothalamus, not in oral ectoderm, was essential for progenitor cell maintenance by regulating LHX3 expression in oral ectoderm via FGF10 expression in the hypothalamus. Convincingly, the phenotype was reversed by the correction of the mutation, and the haploinsufficiency of OTX2 in control iPSCs revealed a similar phenotype, demonstrating that this mutation was responsible. Thus, we established an iPSC-based congenital pituitary disease model, which recapitulated interaction between hypothalamus and oral ectoderm and demonstrated the essential role of hypothalamic OTX2.

    DOI: 10.1172/JCI127378

    Web of Science

    PubMed

  51. Dipeptidyl peptidase-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels in patients with type 2 diabetes: A randomized controlled trial. Reviewed International journal

    Onoue T, Goto M, Wada E, Furukawa M, Okuji T, Okada N, Kobayashi T, Iwama S, Sugiyama M, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Seino Y, Suga H, Banno R, Hamada Y, Ando M, Yamamor E, Arima H

    PloS one   Vol. 15 ( 1 ) page: e0228004   2020.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport.

    DOI: 10.1371/journal.pone.0228004

    Web of Science

    PubMed

  52. Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells. Reviewed International journal

    Kasai T, Suga H, Sakakibara M, Ozone C, Matsumoto R, Kano M, Mitsumoto K, Ogawa K, Kodani Y, Nagasaki H, Inoshita N, Sugiyama M, Onoue T, Tsunekawa T, Takagi H., Hagiwara D., Iwama S., Goto M., Banno R., Takahashi J., Arima H.

    Cell reports   Vol. 30 ( 1 ) page: 18 - +   2020.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The pituitary is a major hormone center that secretes systemic hormones responding to hypothalamus-derived-releasing hormones. Previously, we reported the independent pituitary induction and hypothalamic differentiation of human embryonic stem cells (ESCs). Here, a functional hypothalamic-pituitary unit is generated using human induced pluripotent stem (iPS) cells in vitro. The adrenocorticotropic hormone (ACTH) secretion capacity of the induced pituitary reached a comparable level to that of adult mouse pituitary because of the simultaneous maturation with hypothalamic neurons within the same aggregates. Corticotropin-releasing hormone (CRH) from the hypothalamic area regulates ACTH cells similarly to our hypothalamic-pituitary axis. Our induced hypothalamic-pituitary units respond to environmental hypoglycemic condition in vitro, which mimics a life-threatening situation in vivo, through the CRH-ACTH pathway, and succeed in increasing ACTH secretion. Thus, we generated powerful hybrid organoids by recapitulating hypothalamic-pituitary development, showing autonomous maturation on the basis of interactions between developing tissues.

    DOI: 10.1016/j.celrep.2019.12.009

    Web of Science

    PubMed

  53. Flash glucose monitoring helps achieve better glycemic control than conventional self-monitoring of blood glucose in non-insulin-treated type 2 diabetes: a randomized controlled trial Reviewed International journal

    Eri Wada, Takeshi Onoue, Tomoko Kobayashi, Tomoko Handa, Ayaka Hayase, Masaaki Ito, Mariko Furukawa, Takayuki Okuji, Norio Okada, Shintaro Iwama, Mariko Sugiyama, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Yachiyo Kuwatsuka, Masahiko Ando, Motomitsu Goto, Hiroshi Arima

    BMJ Open Diabetes Research & Care   Vol. 8 ( 1 )   2020.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    INTRODUCTION: The present study aimed to evaluate the effects of flash glucose monitoring (FGM) and conventional self-monitoring of blood glucose (SMBG) on glycemic control in patients with non-insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: In this 24-week, multicenter, open-label, randomized (1:1), parallel-group study, patients with non-insulin-treated type 2 diabetes at five hospitals in Japan were randomly assigned to the FGM (n=49) or SMBG (n=51) groups and were provided each device for 12 weeks. The primary outcome was change in glycated hemoglobin (HbA1c) level, and was compared using analysis of covariance model that included baseline values and group as covariates. RESULTS: Forty-eight participants in the FGM group and 45 in the SMBG group completed the study. The mean HbA1c levels were 7.83% (62.1 mmol/mol) in the FGM group and 7.84% (62.2 mmol/mol) in the SMBG group at baseline, and the values were reduced in both FGM (-0.43% (-4.7 mmol/mol), p<0.001) and SMBG groups (-0.30% (-3.3 mmol/mol), p=0.001) at 12 weeks. On the other hand, HbA1c was significantly decreased from baseline values in the FGM group, but not in the SMBG group at 24 weeks (FGM: -0.46% (-5.0 mmol/mol), p<0.001; SMBG: -0.17% (-1.8 mmol/mol), p=0.124); a significant between-group difference was also observed (difference -0.29% (-3.2 mmol/mol), p=0.022). Diabetes Treatment Satisfaction Questionnaire score was significantly improved, and the mean glucose levels, SD of glucose, mean amplitude of glycemic excursions and time in hyperglycemia were significantly decreased in the FGM group compared with the SMBG group. CONCLUSIONS: Glycemic control was better with FGM than with SMBG after cessation of glucose monitoring in patients with non-insulin-treated type 2 diabetes. TRIAL REGISTRATION NUMBER: UMIN000026452, jRCTs041180082.

    DOI: 10.1136/bmjdrc-2019-001115

    Web of Science

    PubMed

  54. Diagnosis of central diabetes insipidus using a vasopressin radioimmunoassay during hypertonic saline infusion Reviewed International journal

    Takagi H., Hagiwara D., Handa T., Sugiyama M., Onoue T., Tsunekawa T. Ito Y., Iwama S., Goto M., Suga H., Banno R., Takahashi K., Matsui S., Arima H.

    Endocrine Journal   Vol. 67 ( 3 ) page: 267 - 274   2020

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Japan Endocrine Society  

    DOI: 10.1507/endocrj.EJ19-0224

    Web of Science

    PubMed

  55. Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study. International journal

    Tomoko Kobayashi, Shintaro Iwama, Yoshinori Yasuda, Norio Okada, Takayuki Okuji, Masaaki Ito, Takeshi Onoue, Motomitsu Goto, Mariko Sugiyama, Taku Tsunekawa, Hiroshi Takagi, Daisuke Hagiwara, Yoshihiro Ito, Hidetaka Suga, Ryoichi Banno, Kenji Yokota, Tetsunari Hase, Masahiro Morise, Naozumi Hashimoto, Masahiko Ando, Yasushi Fujimoto, Hideharu Hibi, Michihiko Sone, Yuichi Ando, Masashi Akiyama, Yoshinori Hasegawa, Hiroshi Arima

    Journal for immunotherapy of cancer   Vol. 8 ( 2 )   2020

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM). METHODS: A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint. RESULTS: Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05). CONCLUSIONS: In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone. CLINICAL TRIALS REGISTRATION: UMIN000019024.

    DOI: 10.1136/jitc-2020-000779

    Web of Science

    PubMed

  56. GABAB Receptor Signaling in the Mesolimbic System Suppresses Binge-like Consumption of a High-Fat Diet. International journal

    Tsunekawa T, Banno R, Yaginuma H, Taki K, Mizoguchi A, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Bettler B, Arima H

    iScience   Vol. 20   page: 337 - +   2019.10

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Binge eating could contribute to the development of obesity, and previous studies suggest that gamma-aminobutyric acid (GABA) type B receptor (GABABR) signaling is involved in the regulation of binge eating. Here, we show that time-restricted access to a high-fat diet (HFD) induces binge-like eating behavior in wild-type mice. HFD consumption during restricted time was significantly increased in corticostriatal neuron-specific GABABR-deficient mice compared with wild-type mice. Furthermore, the GABABR agonist baclofen suppressed HFD intake during restricted time in wild-type mice but not in corticostriatal or dopaminergic neuron-specific GABABR-deficient mice. In contrast, there were no significant differences in food consumption among genotypes under ad libitum access to HFD. Thus, our data show that the mesolimbic system regulates food consumption under time-restricted but not ad libitum access to HFD and have identified a mechanism by which GABABR signaling suppresses binge-like eating of HFD.

    DOI: 10.1016/j.isci.2019.09.032

    Web of Science

    PubMed

  57. Improved methods for the differentiation of hypothalamic vasopressin neurons using mouse induced pluripotent stem cells. Reviewed International journal

    Mitsumoto K, Suga H, Sakakibara M, Soen M, Yamada T, Ozaki H, Nagai T, Kano M, Kasai T, Ozone C, Ogawa K, Sugiyama M, Onoue T, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Stem Cell Research   Vol. 40   page: 101572 - -   2019.10

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    High differentiation efficiency is one of the most important factors in developing an in vitro model from pluripotent stem cells. In this report, we improved the handling technique applied to mouse-induced pluripotent stem (iPS) cells, resulting in better differentiation into hypothalamic vasopressin (AVP) neurons. We modified the culture procedure to make the maintenance of iPS cells in an undifferentiated state much easier. Three-dimensional floating culture was demonstrated to be effective for mouse iPS cells. We also improved the differentiation method with regards to embryology, resulting in a greater number of bigger colonies of AVP neurons differentiating from mouse iPS cells. Fgf8, which was not used in the original differentiation method, increased iPS differentiation into AVP neurons. These refinements will be useful as a valuable tool for the modeling of degenerative disease in AVP neurons in vitro using disease-specific iPS cells in future studies.

    DOI: 10.1016/j.scr.2019.101572

    Web of Science

    PubMed

  58. Tanycyte-like cells derived from mouse embryonic stem culture show hypothalamic neural stem/progenitor cell functions. Reviewed International journal

    Kano M, Suga H, Ishihara T, Sakakibara M, Soen M, Yamada T, Ozaki H, Mitsumoto K, Kasai T, Sugiyama M, Onoue T, Tsunekawa T, Takagi H, Hagiwara D, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Endoclinology   Vol. 160 ( 7 ) page: 1701 - 1718   2019.7

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Tanycytes have recently been accepted as neural stem/progenitor cells in the postnatal hypothalamus. Persistent retina and anterior neural fold homeobox (Rax) expression is characteristic of tanycytes in contrast to its transient expression of whole hypothalamic precursors. In this study, we found that Rax+ residual cells in the maturation phase of hypothalamic differentiation in mouse embryonic stem cell (mESC) cultures had similar characteristics to ventral tanycytes. They expressed typical neural stem/progenitor cell markers, including Sox2, vimentin, and nestin, and differentiated into mature neurons and glial cells. Quantitative RT-PCR analysis showed that Rax+ residual cells expressed Fgf-10, Fgf-18, and Lhx2, which are expressed by ventral tanycytes. They highly expressed tanycyte-specific genes Dio2 and Gpr50 compared with Rax+ early hypothalamic progenitor cells. Therefore, Rax+ residual cells in the maturation phase of hypothalamic differentiation were considered to be more differentiated and similar to late progenitor cells and tanycytes. They self-renewed and formed neurospheres when cultured with exogenous FGF-2. Additionally, these Rax+ neurospheres differentiated into three neuronal lineages (neurons, astrocytes, and oligodendrocytes), including neuropeptide Y+ neuron, that are reported to be differentiated from ventral tanycytes toward the arcuate nuclei. Thus, Rax+ residual cells were multipotent neural stem/progenitor cells. Rax+ neurospheres were stably passaged and retained high Sox2 expression even after multiple passages. These results suggest the successful induction of Rax+ tanycyte-like cells from mESCs [induced tanycyte-like (iTan) cells]. These hypothalamic neural stem/progenitor cells may have potential in regenerative medicine and as a research tool.

    DOI: 10.1210/en.2019-00105

    Web of Science

    PubMed

  59. Application of pluripotent stem cells for treatment of human neuroendocrine disorders. Reviewed

    Suga H

    Cell and tissue research   Vol. 375 ( 1 ) page: 267 - 278   2019.1

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00441-018-2880-4

    Web of Science

    PubMed

  60. Chemical chaperone 4-phenylbutylate reduces mutant protein accumulation in the endoplasmic reticulum of arginine vasopressin neurons in a mouse model for familial neurohypophysial diabetes insipidus Reviewed

    Tochiya M, Hagiwara D, Azuma Y, Miyata M, Morishita Y, Suga H, Onoue T, Tsunekawa T, Takagi H, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Neuroscience Letters   Vol. 682   page: 50 - 55   2018.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier Ireland Ltd  

    Familial neurohypophysial diabetes insipidus (FNDI), characterized by progressive polyuria and loss of arginine vasopressin (AVP) neurons, is an autosomal dominant disorder caused by AVP gene mutations. Our previous studies with FNDI model mice demonstrated that mutant proteins accumulated in the endoplasmic reticulum (ER) of AVP neurons. Here, we examined therapeutic effects of the chemical chaperone 4-phenylbutylate (4-PBA) in FNDI mice. Treatment with 4-PBA reduced mutant protein accumulation in the ER of FNDI mice and increased AVP release, leading to reduced urine volumes. Furthermore, AVP neuron loss under salt loading was attenuated by 4-PBA treatment. These data suggest that 4-PBA ameliorated mutant protein accumulation in the ER of AVP neurons and thereby prevented FNDI phenotype progression.

    DOI: 10.1016/j.neulet.2018.06.013

    Web of Science

    Scopus

    PubMed

  61. Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing Reviewed

    Hitoshi Kobayashi, Katsumi Ebisawa, Miki Kambe, Takatoshi Kasai, Hidetaka Suga, Kae Nakamura, Yuji Narita, Aika Ogata, Yuzuru Kamei

    Nagoya Journal of Medical Science   Vol. 80 ( 2 ) page: 141 - 153   2018.5

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nagoya University  

    Recently, the effects of stem cell supernatants or exosomes, such as skin wounds, have attracted attention. However, the effects of the induced pluripotent stem (iPS) cell-derived exosomes (iPS-Exos) have not been investigated in detail. Here, we investigated the effects of iPS-Exos on skin wound healing using an animal model. We isolated iPS-Exos from the iPS cell culture media. Control exosomes were isolated from unused iPS cell culture media (M-Exos). We first observed the morphologic characteristics of the isolated exosomes and examined the expression of surface antigens. The effects of these exosomes on the migratory response and proliferation of fibroblasts were analyzed as well. Additionally, using a diabetic ulcer model, the effects of iPS-Exos and M-Exos on skin wound healing were investigated. Transmission electron microscope analysis demonstrated that the size of iPS-Exos (120 ± 25 nm) was significantly larger than that of M-Exos (≤ 100 nm). Flow cytometry analyses showed that iPS-Exos were positive for CD9, CD63, and CD81, whereas they were negative for HLA-ABC and -DR expression. The migratory ability of fibroblasts cocultured with iPS-Exos was shown to be higher than that of the cells cocultured with M-Exos, as demonstrated using scratch assay. Skin wound healing model results showed that the administration of iPS-Exos results in a faster wound closure compared with that observed in the M-Exo group. In conclusion, the results obtained here indicate that iPS-Exos may promote the migration of fibroblasts in vitro and in vivo, suggesting the possibility of using iPS-Exos for the treatment of diabetic ulcer.

    DOI: 10.18999/nagjms.80.2.141

    Scopus

    PubMed

  62. Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing

    Kobayashi Hitoshi, Ebisawa Katsumi, Kambe Miki, Kasai Takatoshi, Suga Hidetaka, Nakamura Kae, Narita Yuji, Ogata Aika, Kamei Yuzuru

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 80 ( 2 ) page: 141 - 153   2018.5

     More details

    Publishing type:Research paper (scientific journal)  

    DOI: 10.18999/nagjms.80.2.141

    Web of Science

  63. Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis Reviewed

    Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y

    Journal of Pathology   Vol. 244 ( 4 ) page: 469 - 478   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:John Wiley and Sons Ltd  

    Autoimmune hypophysitis (AH) is thought to be an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland. Among AH pathologies, lymphocytic infundibulo-neurohypophysitis (LINH) involves infiltration of the neurohypophysis and/or the hypothalamic infundibulum, causing central diabetes insipidus resulting from insufficiency of arginine vasopressin secretion. The pathophysiological and pathogenetic mechanisms underlying LINH are largely unknown. Clinically, differentiating LINH from other pituitary diseases accompanied by mass lesions, including tumours, has often been difficult, because of similar clinical manifestations. We recently reported that rabphilin-3A is an autoantigen and that anti-rabphilin-3A antibodies constitute a possible diagnostic marker for LINH. However, the involvement of rabphilin-3A in the pathogenesis of LINH remains to be elucidated. This study was undertaken to explore the role of rabphilin-3A in lymphocytic neurohypophysitis and to investigate the mechanism. We found that immunization of mice with rabphilin-3A led to neurohypophysitis. Lymphocytic infiltration was observed in the neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice immunized with rabphilin-3A showed an increase in the volume of urine that was hypotonic as compared with control mice. Administration of a cocktail of monoclonal anti-rabphilin-3A antibodies did not induce neurohypophysitis. However, abatacept, which is a chimeric protein that suppresses T-cell activation, decreased the number of T cells specific for rabphilin-3A in peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic infiltration of CD3+ T cells in the neurohypophysis of mice that had been immunized with rabphilin-3A. Additionally, there was a linear association between the number of T cells specific for rabphilin-3A in PBMCs and the number of CD3+ T cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin-3A is a pathogenic antigen, and that T cells specific for rabphilin-3A are involved in the pathogenesis of neurohypophysitis in mice. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp
    Sons, Ltd.

    DOI: 10.1002/path.5046

    Web of Science

    Scopus

    PubMed

  64. Functional Pituitary Tissue Generation from Human Embryonic Stem Cells. Reviewed International journal

    Kano M, Suga H, Kasai T, Ozone C, Arima H

    Current protocols in neuroscience   Vol. 83 ( 1 ) page: e48   2018.4

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    The anterior pituitary gland produces several hormones essential for regulation of the somatic endocrine system. Deficiency of these hormones can cause life-threatening diseases, including adrenal crisis. Pituitary tissue generated from human pluripotent stem cells is expected to provide better treatment than current hormone replacement therapy. During early mammalian development, the pituitary anlage (Rathke's pouch) develops from non-neural ectoderm adjacent to the developing ventral hypothalamus. The close interaction between these two tissues is crucial for Rathke's pouch development and involves several signaling molecules. Early exposure of human embryonic stem cells in 3D floating culture to sonic hedgehog and bone morphogenetic protein 4 promoted the cells' differentiation into oral ectoderm and, subsequently, hormone-producing cells such as corticotrophs (adrenocorticotropic hormone-producing cells). The differentiation approach described herein, which induces the formation of pituitary tissue in contact with hypothalamic neural tissue, mimics mammalian pituitary development. The differentiated corticotrophs are functional, responding normally to both release and feedback signals. © 2018 by John Wiley & Sons, Inc.

    DOI: 10.1002/cpns.48

    PubMed

  65. Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. Reviewed International journal

    Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Yokota K, Hase T, Morise M, Hashimoto N, Ando M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H

    Journal of the Endocrine Society   Vol. 2 ( 3 ) page: 241 - 251   2018.3

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    Context: Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. Objective: This study examined the incidence of endocrine irAEs induced by nivolumab. Patients and Main Outcome Measured: Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Results: Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti-thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Conclusions: Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

    DOI: 10.1210/js.2017-00432

    Web of Science

    PubMed

  66. Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors Reviewed

    Ogawa K, Suga H, Ozone C, Sakakibara M, Yamada T, Kano M, Mitsumoto K, Kasai T, Kodani Y, Nagasaki H, Yamamoto N, Hagiwara D, Goto M, Banno R, Sugimura Y, Arima H

    Scientific Reports   Vol. 8 ( 1 ) page: 3615   2018.2

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Publishing Group  

    Arginine-vasopressin (AVP) neurons exist in the hypothalamus, a major region of the diencephalon, and play an essential role in water balance. Here, we established the differentiation method for AVP-secreting neurons from human embryonic stem cells (hESCs) by recapitulating in vitro the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors. Secondly, the induced AVP neurons were identified by immunohistochemistry and these neurons secreted AVP after potassium chloride stimulation. Additionally, other hypothalamic neuropeptides were also detected, such as oxytocin, corticotropin-releasing hormone, thyrotropin-releasing hormone, pro-opiomelanocortin, agouti-related peptide, orexin, and melanin-concentrating hormone. This is the first report describing the generation of secretory AVP neurons derived from hESCs. This method will be applicable to research using disease models and, potentially, for regenerative medicine of the hypothalamus.

    DOI: 10.1038/s41598-018-22053-x

    Web of Science

    Scopus

    PubMed

  67. Sequestosome 1 (SQSTMI/p62) maintains protein folding capacity under endoplasmic reticulum stress in mouse hypothalamic organotypic culture Reviewed

    Tominaga T, Goto M, Onoue T, Mizoguchi A, Sugiyama M, Tsunekawa T, Hagiwara D, Morishita Y, Ito Y, Iwama S, Suga H, Banno R, ArimaH

    NEUROSCIENCE LETTERS   Vol. 656   page: 103 - 107   2017.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER IRELAND LTD  

    Sequestosome 1 (SQSTM1) also known as ubiquitin-binding protein p62 (p62) is a cargo protein involved in the degradation of misfolded proteins via selective autophagy. Disruption of autophagy and resulting accumulation of misfolded proteins in the endoplasmic reticulum (ER) leads to ER stress. ER stress is implicated in several neurodegenerative diseases and obesity. As knockout of p62 (p62KO) reportedly induces obesity in mice, we examined how p62 contributes to ER stress and the ensuing unfolded protein response (UPR) in hypothalamus using mouse organotypic cultures in the present study. Cultures from p62KO mice showed significantly reduced formation of LC3-GFP puncta, an index of autophagosome formation, in response to the chemical ER stressor thapsigargin compared to wild-type (WT) cultures. Hypothalamic cultures from p62KO mice exhibited higher basal expression of the UPR/ER stress markers CHOP mRNA and ATF4 mRNA than WT cultures. Thapsigargin enhanced CHOP, ATF4, and BiP mRNA as well as p-elF2 alpha protein expression in both NWT and p62KO cultures, but all peak values were greater in p621(0 cultures. A proteasome inhibitor increased p62 expression in WT cultures and upregulated the UPR/ER stress markers CHOP mRNA and ATF4 mRNA in both genotypes, but to a greater extent in p62KO cultures. Therefore, p62 deficiency disturbed autophagosome formation and enhanced both basal and chemically induced ER stress, suggesting that p62 serves to prevent ER stress in mouse hypothalamus by maintaining protein folding capacity. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.neulet.2017.06.014

    Web of Science

    PubMed

  68. PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions Reviewed

    Sugiyama M., Banno R., Mizoguchi A., Tominaga T., Tsunekawa T., Onoue T., Hagiwara D., Ito Y., Morishita Y., Iwama S., Goto M., Suga H., Arima H.

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 488 ( 1 ) page: 116 - 121   2017.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Hypothalamic insulin receptor signaling regulates energy balance and glucose homeostasis via agouti related protein (AgRP). While protein tyrosine phosphatase 1B (PTP1B) is classically known to be a negative regulator of peripheral insulin signaling by dephosphorylating both insulin receptor beta (IR beta) and insulin receptor substrate, the role of PTP1B in hypothalamic insulin signaling remains to be fully elucidated. In the present study, we investigated the role of PTP1B in hypothalamic insulin signaling using PTP1B deficient (KO) mice in vivo and ex vivo. For the in vivo study, hypothalamic insulin resistance induced by a high-fat diet (HFD) improved in KO mice compared to wild-type (WT) mice. Hypothalamic AgRP mRNA expression levels were also significantly decreased in KO mice independent of body weight changes. In an ex vivo study using hypothalamic organotypic cultures, insulin treatment significantly increased the phosphorylation of both IR beta and Akt in the hypothalamus of KO mice compared to WT mice, and also significantly decreased AgRP mRNA expression levels in KO mice. While incubation with inhibitors of phosphatidylinositol-3 kinase (PI3K) had no effect on basal levels of Akt phosphorylation, these suppressed insulin induction of Akt phosphorylation to almost basal levels in WT and KO mice. The inhibition of the PI3K-Akt pathway blocked the downregulation of AgRP mRNA expression in KO mice treated with insulin. These data suggest that PTP1B acts on the hypothalamic insulin signaling via the PI3K-Akt pathway. Together, our results suggest a deficiency of PTP1B improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under HFD conditions. (C) 2017 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2017.05.019

    Web of Science

    PubMed

  69. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis Reviewed

    Iwata N., Iwama S., Sugimura Y., Yasuda Y., Nakashima K., Takeuchi S., Hagiwara D., Ito Y., Suga H., Goto M., Banno R., Caturegli P., Koike T., Oshida Y., Arima H.

    PITUITARY   Vol. 20 ( 3 ) page: 301 - 310   2017.6

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    Purpose IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear.
    Methods In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects.We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence.
    Results APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases.
    Conclusions Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

    DOI: 10.1007/s11102-016-0780-8

    Web of Science

    PubMed

  70. Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia Reviewed International journal

    Tsunekawa T, Banno R, Mizoguchi A, Sugiyama M, Tominaga T, Onoue T, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Sugimura Y, Arima H

    EBIOMEDICINE   Vol. 16   page: 172 - 183   2017.2

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ELSEVIER SCIENCE BV  

    Protein tyrosine phosphatase 1B (PTP1B) regulates leptin signaling in hypothalamic neurons via the JAK2-STAT3 pathway. PTP1B has also been implicated in the regulation of inflammation in the periphery. However, the role of PTP1B in hypothalamic inflammation, which is induced by a high-fat diet (HFD), remains to be elucidated. Here, we showed that STAT3 phosphorylation (p-STAT3) was increased in microglia in the hypothalamic arcuate nucleus of PTP1B knock-out mice (KO) on a HFD, accompanied by decreased Tnf and increased Il10 mRNA expression in the hypothalamus compared to wild-type mice (WT). In hypothalamic organotypic cultures, incubation with TNF alpha led to increased p-STAT3, accompanied by decreased Tnf and increased Il10 mRNA expression, in KO compared to WT. Incubation with p-STAT3 inhibitors or microglial depletion eliminated the differences in inflammation between genotypes. These data indicate an important role of JAK2-STAT3 signaling negatively regulated by PTP1B in microglia, which attenuates hypothalamic inflammation under HFD conditions. (C) 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    DOI: 10.1016/j.ebiom.2017.01.007

    Web of Science

    PubMed

  71. Functional pituitary tissue formation Reviewed International journal

    Chikafumi Ozone, Hidetaka Suga

    Methods in Molecular Biology   Vol. 1597   page: 57 - 65   2017

     More details

    Language:English   Publishing type:Part of collection (book)   Publisher:Humana Press Inc.  

    The adenohypophysis, which mainly consists of anterior pituitary, plays important roles for endocrine systems by secreting several hormones indispensable for maintaining homeostasis. During early mouse development, the pituitary primordium (called Rathke’s pouch) develops from oral ectoderm adjacent to ventral hypothalamus by interaction between these two tissues. By using mouse embryonic stem cells (ESCs), we recapitulated this in vivo micro-environment of the pituitary development and demonstrated that Rathke’s pouch-like structures were self-formed from three-dimensional (3D) floating culture. The mouse ESC-derived Rathke’s pouch-like structures subsequently differentiated into hormone-producing cells such as corticotrophs and somatotrophs. We have modified this technique for human pluripotent stem cells and recently reported that pituitary placodes can also be generated from human ESCs through a similar process. Here, we describe a protocol for human ESC culture for in vitro generation of 3D pituitary tissue.

    DOI: 10.1007/978-1-4939-6949-4_5

    Web of Science

    Scopus

    PubMed

  72. Making pituitary hormone-producing cells in a dish.

    Hidetaka Suga

    Endocrine Journal   Vol. 63 ( 8 ) page: 669-680   2016.8

     More details

    Language:English  

    DOI: 10.1507/endocrj.EJ16-0232

  73. Recapitulating Hypothalamus and Pituitary Development Using Embryonic Stem/Induced Pluripotent Stem Cells.

    Hidetaka Suga

    Research and Perspectives in Endocrine Interactions (Stem Cells in Neuroendocrinology)     page: 35-50   2016.8

     More details

    Language:English  

    DOI: 10.1007/978-3-319-41603-8

  74. Differentiation of pluripotent stem cells into hypothalamic and pituitary cells. Reviewed

    Hidetaka Suga

    Neuroendocrinology   Vol. 101   page: 18-24   2015.4

     More details

    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  75. 劇症1型糖尿病を合併した薬剤性過敏症症候群の1例

    落合啓史、岡嵜裕子、尾方秀忠、須賀英隆、恒川新、大磯ユタカ

    日本内科学会雑誌   Vol. 103 ( 5 ) page: 1183-1186   2014.5

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)  

  76. Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus.

    Hagiwara D, Arima H, Morishita Y, Wenjun L, Azuma Y, Ito Y, Suga H, Goto M, Banno R, Sugimura Y, Shiota A, Asai N, Takahashi M, Oiso Y.

    Cell Death Dis.   Vol. 5   page: e1148   2014

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  77. Mitogen-activated protein kinase phosphatase 1 negatively regulates MAPK signaling in mouse hypothalamus.

    Adachi K, Goto M, Onoue T, Tsunekawa T, Shibata M, Hagimoto S, Ito Y, Banno R, Suga H, Sugimura Y, Oiso Y, Arima H.

    Neurosci Lett.   Vol. 569   page: 49-54   2014

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  78. Minocycline prevents osmotic demyelination associated with aquaresis.

    Takagi H, Sugimura Y, Suzuki H, Iwama S, Izumida H, Fujisawa H, Ogawa K, Nakashima K, Ochiai H, Takeuchi S, Kiyota A, Suga H, Goto M, Banno R, Arima H, Oiso Y.

    Kidney Int.   Vol. 86 ( 5 ) page: 954-964   2014

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  79. Activating transcription factor 6α is required for the vasopressin neuron system to maintain water balance under dehydration in male mice.

    Azuma Y, Hagiwara D, Lu W, Morishita Y, Suga H, Goto M, Banno R, Sugimura Y, Oyadomari S, Mori K, Shiota A, Asai N, Takahashi M, Oiso Y, Arima H.

    Endocrinology   Vol. 155 ( 12 ) page: 4905-4914   2014

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  80. GABA type B receptor signaling in proopiomelanocortin neurons protects against obesity, insulin resistance, and hypothalamic inflammation in male mice on a high-fat diet.

    Ito Y, Banno R, Shibata M, Adachi K, Hagimoto S, Hagiwara D, Ozawa Y, Goto M, Suga H, Sugimura Y, Bettler B, Oiso Y. Arima H.

    J Neurosci   Vol. 33 ( 43 ) page: 17166-171673   2013

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  81. Expression of neuropeptide Y and agouti-related protein mRNA stimulated by glucocorticoids is attenuated via NF-κB p65 under ER stress in mouse hypothalamic cultures.

    Hagimoto S, Arima H, Adachi K, Ito Y, Suga H, Sugimura Y, Goto M, Banno R, Oiso Y.

    Neurosci Lett.   Vol. 553   page: 165-169   2013

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  82. In vitro organogenesis in three dimensions: self-organising stem cells.

    Sasai Y, Eiraku M, Suga H.

    Development.   Vol. 139 ( 22 ) page: 4111-4121   2012

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1242/dev.079590.

  83. Self-formation of functional adenohypophysis in three-dimensional culture.

    Suga H, Kadoshima T, Minaguchi M, Ohgushi M, Soen M, Nakano T, Takata N, Wataya T, Muguruma K, Miyoshi H, Yonemura S, Oiso Y, Sasai Y.

    Nature.   Vol. 480 ( 7375 ) page: 57-62.   2011

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/nature10637.

  84. Molecular pathway and cell state responsible for dissociation-induced apoptosis in human pluripotent stem cells.

    Ohgushi M, Matsumura M, Eiraku M, Murakami K, Aramaki T, Nishiyama A, Muguruma K, Nakano T, Suga H, Ueno M, Ishizaki T, Suemori H, Narumiya S, Niwa H, Sasai Y.

    Cell Stem Cell.   Vol. 7 ( 2 ) page: 225-239.   2010

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  85. Urokinase-type plasminogen activator receptor is associated with the development of adipose tissue.

    Kanno Y, Matsuno H, Kawashita E, Okada K, Suga H, Ueshima S, Matsuo O.

    Thromb Haemost.   Vol. 104 ( 6 ) page: 1124-32.   2010

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  86. Inflammatory cytokines regulate glycoprotein subunit beta5 of thyrostimulin through nuclear factor-kappaB.

    Suzuki C, Nagasaki H, Okajima Y, Suga H, Ozaki N, Arima H, Iwasaki Y, Oiso Y

    Endocrinology.   Vol. 150 ( 5 ) page: 2237-2243.   2009

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  87. Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha2 (GPA2) and beta5 (GPB5).

    Okajima Y, Nagasaki H, Suzuki C, Suga H, Ozaki N, Arima H, Hamada Y, Civelli O, Oiso Y.

    Regul Pept.   Vol. 148 ( 1-3 ) page: 62-67.   2008

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  88. Novel treatment for lithium induced nephrogenic diabetes insipidus rat model using the sendai-virus vector carrying aquaporin 2 gene.

    Suga H, Nagasaki H, Kondo TA, Okajima Y, Suzuki C, Ozaki N, Arima H, Yamamoto T, Ozaki N, Akai M, Sato A, Uozumi N, Inoue M, Hasegawa M, Oiso Y.

    Endocrinology.   Vol. 149 ( 11 ) page: 5803-5810   2008

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  89. The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin.

    Suzuki C, Nagasaki H, Okajima Y, Suga H, Arima H, Iwasaki Y, Oiso Y.

    Regul Pept.   Vol. 142 ( 1-2 ) page: 60-67.   2007

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  90. Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions.

    Kanno Y, Hirade K, Ishisaki A, Nakajima K, Suga H, Into T, Matsushita K, Okada K, Matsuo O, Matsuno H.

    J Thromb Haemost.   Vol. 4 ( 7 ) page: 1602-1610.   2006

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  91. Differential roles of MAP kinases in atorvastatin-induced VEGF release in cardiac myocytes.

    Nakajima K, Suga H, Matsuno H, Ishisaki A, Hirade K, Kozawa O.

    Life Sci.   Vol. 79 ( 12 ) page: 1214-1220.   2006

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  92. Akt regulates thrombin-induced HSP27 phosphorylation in aortic smooth muscle cells: function at a point downstream from p38 MAP kinase.

    Nakajima K, Hirade K, Ishisaki A, Matsuno H, Suga H, Kanno Y, Shu E, Kitajima Y, Katagiri Y, Kozawa O.

    Life Sci.   Vol. 77 ( 1 ) page: 96-107   2005

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  93. Midazolam suppresses thrombin-induced heat shock protein 27 phosphorylation through inhibition of p38 mitogen-activated protein kinase in cardiac myocytes.

    Tanabe K, Akamatsu S, Suga H, Takai S, Kato K, Dohi S, Kozawa O.

    J Cell Biochem.   Vol. 96 ( 1 ) page: 56-64.   2005

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  94. alphaB-crystallin is phosphorylated during myocardial infarction: involvement of platelet-derived growth factor-BB.

    Shu E, Matsuno H, Akamastu S, Kanno Y, Suga H, Nakajima K, Ishisaki A, Takai S, Kato K, Kitajima Y, Kozawa O.

    Arch Biochem Biophys.   Vol. 438 ( 2 ) page: 111-118.   2005

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  95. Possible involvement of phosphatidylinositol 3-kinase/Akt signal pathway in vasopressin-induced HSP27 phosphorylation in aortic smooth muscle A10 cells.

    Suga H, Nakajima K, Shu E, Kanno Y, Hirade K, Ishisaki A, Matsuno H, Tanabe K, Takai S, Akamatsu S, Kato K, Oiso Y, Kozawa O.

    Arch Biochem Biophys.   Vol. 438 ( 2 ) page: 137-145.   2005

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  96. Vasopressin phosphorylates HSP27 in aortic smooth muscle cells.

    Akamatsu S, Nakajima K, Ishisaki A, Matsuno H, Tanabe K, Takei M, Takenaka M, Hirade K, Yoshimi N, Suga H, Oiso Y, Kato K, Kozawa O.

    J Cell Biochem.   Vol. 92 ( 6 ) page: 1203-1211.   2004

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  97. Possible involvement of p44/p42 MAP kinase in retinoic acid-stimulated vascular endothelial growth factor release in aortic smooth muscle cells.

    Tanabe K, Hirade K, Ishisaki A, Shu E, Suga H, Kitajima Y, Katagiri Y, Dohi S, Kozawa O.

    Atherosclerosis.   Vol. 175 ( 2 ) page: 245-251.   2004

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  98. Adrenal pseudocyst mimicking a pheochromocytoma found after a traffic accident.

    Suga H, Inagaki A, Ota K, Taguchi S, Kato T, Kakiya S, Itatsu T, Yokoi K, Tsuzuki T.

    Intern Med.   Vol. 42 ( 1 ) page: 66-71.   2003

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

  99. Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy.

    Sato T, Inagaki A, Uchida K, Ueki T, Goto N, Matsuoka S, Katayama A, Haba T, Tominaga Y, Okajima Y, Ohta K, Suga H, Taguchi S, Kakiya S, Itatsu T, Kobayashi T, Nakao A.

    Transplantation.   Vol. 76 ( 9 ) page: 1320-1326.   2003

     More details

    Language:English   Publishing type:Research paper (scientific journal)  

▼display all

Books 23

  1. オルガノイドがもたらすライフサイエンス革命 あなたの研究に、どう使う? 進化と深化を生む未来型研究30選(実験医学増刊Vol.42 No.5)

    須賀英隆、有馬寛( Role: Contributor ,  内分泌系オルガノイド―下垂体オルガノイドを中心に)

    羊土社  2024.3  ( ISBN:978-4-7581-0417-3

     More details

    Language:Japanese

  2. オルガノイドがもたらすライフサイエンス革命 あなたの研究に、どう使う? 進化と深化を生む未来型研究30選(実験医学増刊 Vol.42 No.5)

    須賀英隆, 有馬寛( Role: Contributor ,  内分泌系オルガノイド―下垂体オルガノイドを中心に)

    羊土社  2024.3 

     More details

    Language:Japanese

  3. ここが知りたい! 内分泌疾患診療ハンドブック Ver.3

    須賀英隆, 岩間信太郎, 有馬寛( Role: Joint author ,  下垂体炎)

    中外医学社  2023.1 

     More details

    Language:Japanese

  4. 最先端ナノライフシステム研究(最先端ナノライフシステム研究編集委員会編)

    須賀英隆( Role: Contributor ,  視床下部-下垂体の再生医療)

    丸善プラネット  2022.3 

     More details

    Language:Japanese

  5. 下垂体・視床下部オルガノイド

    加納麻弓子,須賀英隆( Role: Joint author)

    実験医学別冊 決定版オルガノイド実験スタンダード:開発者直伝!珠玉のプロトコール集(羊土社)  2019.3 

     More details

    Language:Japanese

  6. 実験医学別冊 決定版オルガノイド実験スタンダード:開発者直伝!珠玉のプロトコール集

    加納 麻弓子, 須賀 英隆( Role: Joint author ,  下垂体・視床下部オルガノイド)

    羊土社  2019.3 

     More details

    Language:Japanese

  7. 中枢性尿崩症

    須賀英隆,髙木博史,有馬寛( Role: Joint author)

    分泌Up To Date、内科(南江堂)  2019 

     More details

    Language:Japanese

  8. Organ Regeneration 3D Stem Cell Culture & Manipulation

    Chikafumi Ozone, Hidetaka Suga( Role: Contributor ,  Functional Pituitary Tissue Formation)

    Springer  2017.7 

     More details

    Language:Japanese

  9. Organ Regeneration Based on Developmental Biology

    Hidetaka Suga, Chikafumi Ozone( Role: Contributor ,  Functional Pituitary Tissue Formation Recapitulating Hypothalamus and Pituitary Decelopment Using ES/iPS Cells)

    Springer  2017.4 

     More details

    Language:Japanese

  10. 下垂体疾患診療マニュアル改訂第2版

    須賀 英隆( Role: Sole author ,  ES/iPS細胞による下垂体分化とその応用)

    診断と治療社  2016.11 

     More details

    Language:Japanese

  11. Medio・多能性幹細胞を用いた視床下部・下垂体研究

    大曽根親文、須賀英隆( Role: Joint author)

    メジカルビュー社  2016.8 

     More details

    Language:Japanese Book type:Scholarly book

  12. クッシング症候群診療マニュアル改訂第2版・ES細胞から下垂体ACTH産生細胞への分化誘導

    大曽根親文,須賀英隆( Role: Joint author)

    診断と治療社  2015.12 

     More details

    Total pages:324   Language:Japanese Book type:Scholarly book

  13. Fluid Management Renaissance ・ヒト多能性幹細胞から機能的な頭部プラコードへの分化誘導

    須賀英隆( Role: Joint author)

    メディカルレビュー社  2015.1 

     More details

    Language:Japanese

  14. 医学の歩み・iPS細胞研究最前線 疾患モデルから臓器再生まで(Vol.9)iPS細胞を用いた視床下部・下垂体の再生に向けて.

    須賀英隆( Role: Joint author)

    医歯薬出版株式会社  2014.12 

     More details

    Language:Japanese

  15. 現代医学.特集/再生医療の現状と課題 多能性幹細胞から視床下部・下垂体への分化.

    須賀英隆.大磯ユタカ( Role: Joint author)

    愛知県医師会  2013.12 

     More details

    Language:Japanese

  16. 最新医学.トップランナーに聞く 内分泌における新しい領域開拓を目指して

    須賀英隆( Role: Joint author)

    最新医学社  2013.3 

     More details

    Language:Japanese

  17. 内分泌・糖尿病・代謝内科・話題 マウスES細胞から機能的下垂体組織の自己形成

    須賀英隆, 大磯ユタカ( Role: Joint author)

    科学評論社  2013.2 

     More details

    Language:Japanese

  18. ホルモンと臨床 ・ 特集/下垂体疾患最前線 ES細胞からの機能的下垂体形成.

    須賀英隆( Role: Joint author)

    医学の世界社  2012.10 

     More details

    Language:Japanese

  19. 遺伝子医学MOOK・ 最新疾患モデルと創薬応用研究、細胞医薬創製研究の最前線 ES細胞からの機能的な脳下垂体組織の形成:医学応用への展望

    須賀英隆( Role: Joint author)

    メディカル ドゥ  2012.7 

     More details

    Language:Japanese

  20. 実験医学・臨床に向けた戦略と最前線~創薬・多細胞体構築に向けて ES細胞から機能的な下垂体の立体形成

    須賀英隆( Role: Joint author)

    羊土社  2012.6 

     More details

    Language:Japanese

  21. ACTH RELATED PEPTIDES.HPA系の基礎研究Update マウスES細胞立体培養におけるラトケ嚢形成とホルモン産生細胞への分化

    須賀英隆,大磯ユタカ,笹井芳樹( Role: Joint author)

    間脳・下垂体・副腎系研究会  2012.3 

     More details

    Language:Japanese

  22. ホルモンと臨床・【内分泌 興味ある症例】 副腎 化学療法が無効で,内照射治療により腫瘍抑制が得られた悪性褐色細胞腫の1例

    田口晴子, 稲垣朱実, 岡島由樹, 深見亜矢子, 太田貴美子, 須賀英隆, 加藤朋子, 垣屋聡, 板津武晴, 佐藤公治, 氏平伸子, 都築豊徳, 横山邦彦.( Role: Joint author)

    医学の世界社  2004.8 

     More details

    Language:Japanese

  23. 新薬と臨床・当院における1型糖尿病に対する超速効型インスリン(Insulin Lispro)の使用経験

    田口晴子, 稲垣朱実, 垣屋聡, 太田貴美子, 須賀英隆, 加藤朋子, 板津武晴, 三輪雅一, 高槻健介( Role: Joint author)

    医薬情報研究所  2002.9 

     More details

    Language:Japanese

▼display all

MISC 34

  1. ナノ量子センサーを用いたiPS細胞由来再生脳オルガノイド機能解明

    徳永真登, 湯川博, 湯川博, 湯川博, 湯川博, 湯川博, 西村勇姿, 須賀英隆, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信

    日本再生医療学会総会(Web)   Vol. 21st   2022

     More details

  2. SIADH(抗利尿ホルモン不適切分泌症候群)

    須賀英隆, 有馬寛

    内分泌疾患・糖尿病・代謝疾患―診療のエッセンス 日本医師会雑誌   Vol. 150 ( 特別号(2) ) page: S93 - S95   2021.10

     More details

    Authorship:Lead author   Language:Japanese  

  3. 【内分泌疾患2】(Part 2)どこまでを専門家がみて,どこから総合内科医がみるのか? 下垂体 中枢性尿崩症,SIADH

    須賀 英隆, 高木 博史, 有馬 寛

    Hospitalist   Vol. 9 ( 2 ) page: 417 - 423   2021.6

     More details

    Authorship:Lead author  

  4. In vitro分化誘導法を用いた視床下部神経幹細胞の再生

    加納麻弓子, 須賀英隆, 有馬寛

    日本下垂体研究会誌   Vol. 8   page: 17 - 18   2021.3

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (other)  

  5. 下垂体オルガノイドによるマイ・メディシン

    須賀英隆, 有馬寛

    医学のあゆみ   Vol. 276 ( 6 ) page: 654 - 661   2021.2

     More details

    Authorship:Lead author   Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  6. The elucidation of functions of iPS cell-derived regenerative brain organoid by quantum-nano sensor

    徳永真登, 湯川博, 三輪田勤, 須賀英隆, 有馬寛, 西村勇姿, 馬場嘉信

    日本化学会春季年会講演予稿集(Web)   Vol. 101st   2021

     More details

  7. The elucidation of functions of iPS cell-derived regenerative brain organoid by quantum-nano sensor

    徳永真登, 湯川博, 三輪田勤, 須賀英隆, 有馬寛, 西村勇姿, 馬場嘉信

    JSMI Report   Vol. 14 ( 2 )   2021

     More details

  8. ナノ量子センサーを用いたiPS細胞由来再生脳オルガノイド機能解明

    徳永真登, 湯川博, 西村勇姿, 須賀英隆, 馬場嘉信

    Organ Biology (Web)   Vol. 28 ( 3 )   2021

     More details

  9. ナノ量子センサーを用いたiPS細胞由来再生脳オルガノイド機能解明

    徳永真登, 湯川博, 三輪田勤, 須賀英隆, 有馬寛, 西村勇姿, 馬場嘉信

    日本再生医療学会総会(Web)   Vol. 20th   2021

     More details

  10. ナノ量子センサーを用いたiPS細胞由来再生脳オルガノイド機能解明

    徳永真登, 湯川博, 湯川博, 湯川博, 湯川博, 西村勇姿, 須賀英隆, 馬場嘉信, 馬場嘉信, 馬場嘉信, 馬場嘉信

    中部化学関係学協会支部連合秋季大会講演予稿集   Vol. 52nd (CD-ROM)   2021

     More details

  11. バソプレシンニューロンにおいて異常タンパク凝集体は小胞体から輸送隔離されることなく小胞体内部で分解される-家族性中枢性尿崩症モデルマウスを用いた検討-

    宮田崇, 萩原大輔, 津村哲郎, 蓬臺優一, 川口頌平, 栗本隼樹, 高木博史, 須賀英隆, 川上奈津子, 坂本浩隆, 松本真実, 大野伸彦, 大野伸彦, 有馬寛

    日本内分泌学会雑誌   Vol. 97 ( 1 )   2021

     More details

  12. iPS細胞由来の下垂体オルガノイドを用いたホルモン補充療法

    多賀詩織, 須賀英隆, 木村徹, 有馬寛

    Drug Delivery System   Vol. 35 ( 4 ) page: 285 - 292   2020.9

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  13. 中枢性尿崩症

    須賀英隆, 髙木博史, 有馬寛

    内科(特集:内分泌Up To Date)   Vol. 124 ( 6 ) page: 2441 - 2444   2019.11

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  14. 下垂体発生における視床下部-口腔外胚葉間FGFの役割

    松本 隆作, 青井 貴之, 小柳 三千代, 須賀 英隆, 福岡 秀規, 井口 元三, 小川 渉, 高橋 裕

    日本内分泌学会雑誌   Vol. 95 ( 1 ) page: 352 - 352   2019.4

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:(一社)日本内分泌学会  

  15. 下垂体発生における視床下部-口腔外胚葉間FGFの役割

    松本 隆作, 青井 貴之, 小柳 三千代, 須賀 英隆, 福岡 秀規, 井口 元三, 小川 渉, 高橋 裕

    日本内分泌学会雑誌   Vol. 95 ( 1 ) page: 408 - 408   2019.4

     More details

    Language:Japanese   Publisher:(一社)日本内分泌学会  

  16. 視床下部と下垂体とのハイブリッド

    須賀英隆, 有馬寛

    月刊細胞   Vol. 51 ( 4 ) page: 20 - 24   2019.3

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  17. マウスES細胞由来‐視床下部細胞の高純度培養法の確立

    小谷侑, 須賀英隆, 山本直樹, 金子葉子, 河田美穂, 中島昭, 長崎弘

    日本生理学雑誌(Web)   Vol. 81 ( 1 ) page: WEB ONLY - 21   2019.2

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    J-GLOBAL

  18. Chemical chaperone 4-phenylbutylate reduces mutant protein accumulation in the endoplasmic reticulum of arginine vasopressin neurons in a mouse model for familial neurohypophysial diabetes insipidus. Reviewed

    Tochiya M, Hagiwara D, Azuma Y, Miyata T, Morishita Y, Suga H, Onoue T, Tsunekawa T, Takagi H, Ito Y, Iwama S, Goto M, Banno R, Arima H

    Neuroscience letters   Vol. 682   page: 50-55   2018.8

  19. Application of pluripotent stem cells for treatment of human neuroendocrine disorders. Reviewed

    Suga H

    Cell and tissue research     2018.8

  20. Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic neurohypophysitis. Reviewed

    Yasuda Y, Iwama S, Kiyota A, Izumida H, Nakashima K, Iwata N, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Enomoto A, Takahashi M, Arima H, Sugimura Y

    The Journal of pathology   Vol. 244 ( 4 ) page: 469-478   2018.4

     More details

  21. Functional Pituitary Tissue Generation from Human Embryonic Stem Cells. Reviewed International journal

    Kano M, Suga H, Kasai T, Ozone C, Arima H

    Current protocols in neuroscience   Vol. 83 ( 1 ) page: e48   2018.4

     More details

  22. 転写因子OTX2は視床下部からのFGFシグナルを介して下垂体を分化させる International journal

    松本 隆作, 須賀 英隆, 井口 元三, 福岡 秀規, 長谷川 奉延, 六車 恵子, 小川 渉, 青井 貴之, 高橋 裕

    日本内分泌学会雑誌   Vol. 94 ( 1 ) page: 314 - 314   2018.4

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:(一社)日本内分泌学会  

  23. Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. Reviewed

    Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T, Takagi H, Hagiwara D, Ito Y, Morishita Y, Goto M, Suga H, Banno R, Yokota K, Hase T, Morise M, Hashimoto N, Ando M, Kiyoi H, Gotoh M, Ando Y, Akiyama M, Hasegawa Y, Arima H

    Journal of the Endocrine Society   Vol. 2 ( 3 ) page: 241-251   2018.3

     More details

  24. Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors. Reviewed

    Ogawa K, Suga H, Ozone C, Sakakibara M, Yamada T, Kano M, Mitsumoto K, Kasai T, Kodani Y, Nagasaki H, Yamamoto N, Hagiwara D, Goto M, Banno R, Sugimura Y, Arima H

    Scientific reports   Vol. 8 ( 1 ) page: 3615   2018.2

  25. 下垂体の立体組織構築

    笠井貴敏, 須賀英隆

    医学のあゆみ   Vol. 264 ( 8 ) page: 653 - 658   2018.2

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

  26. マウス胚性幹細胞由来‐視床下部組織におけるMCHニューロンの特徴づけ

    小谷侑, 須賀英隆, 金子葉子, 中島昭, 長崎弘

    日本神経内分泌学会学術集会プログラム・抄録集   Vol. 45th   page: 50   2018

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    J-GLOBAL

  27. バソプレシンニューロンにおける異常蛋白の処理機構に小胞体シャペロンBiPおよびライソソームが関与する

    宮田崇, 萩原大輔, 萩原大輔, 川口頌平, 栗本隼樹, 尾崎創, 光本一樹, 高木博史, 須賀英隆, 坂本浩隆, 有馬寛

    バゾプレシン研究会プログラム・講演抄録   Vol. 29th   2018

     More details

  28. マウスES細胞由来視床下部神経の同種移植

    長崎弘, 小谷侑, 須賀英隆, 金子葉子

    バゾプレシン研究会プログラム・講演抄録   Vol. 28th   page: 12   2017.12

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    J-GLOBAL

  29. マウス胚性幹細胞由来AVP神経の電気生理学的特性

    金子葉子, 大熊真人, 小谷侑, 須賀英隆, 中島昭, 宮地栄一, 長崎弘

    日本神経内分泌学会学術集会プログラム・抄録集   Vol. 44th ( 4 ) page: 43 - 1227   2017.12

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:(一社)日本内分泌学会  

    J-GLOBAL

  30. 疾患特異的iPS細胞を用いたLHX4異常症の発症機序の解明

    松本 隆作, 須賀 英隆, 青井 貴之, 高木 優樹, 石井 智弘, 長谷川 奉延, 六車 恵子, 小川 渉, 高橋 裕

    日本内分泌学会雑誌   Vol. 93 ( 2 ) page: 537 - 537   2017.10

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:(一社)日本内分泌学会  

  31. Sequestosome 1 (SQSTM1/p62) maintains protein folding capacity under endoplasmic reticulum stress in mouse hypothalamic organotypic culture. Reviewed

    Tominaga T, Goto M, Onoue T, Mizoguchi A, Sugiyama M, Tsunekawa T, Hagiwara D, Morishita Y, Ito Y, Iwama S, Suga H, Banno R, Arima H

    Neuroscience letters   Vol. 656   page: 103-107   2017.8

  32. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis. Reviewed

    Iwata N, Iwama S, Sugimura Y, Yasuda Y, Nakashima K, Takeuchi S, Hagiwara D, Ito Y, Suga H, Goto M, Banno R, Caturegli P, Koike T, Oshida Y, Arima H

    Pituitary   Vol. 20 ( 3 ) page: 301-310   2017.6

  33. PTP1B deficiency improves hypothalamic insulin sensitivity resulting in the attenuation of AgRP mRNA expression under high-fat diet conditions. Reviewed

    Sugiyama M, Banno R, Mizoguchi A, Tominaga T, Tsunekawa T, Onoue T, Hagiwara D, Ito Y, Morishita Y, Iwama S, Goto M, Suga H, Arima H

    Biochemical and biophysical research communications   Vol. 488 ( 1 ) page: 116-121   2017.6

  34. 疾患特異的iPS細胞を用いた先天性下垂体機能低下症の病態解明

    松本 隆作, 須賀 英隆, 青井 貴之, 坂東 弘教, 福岡 秀規, 井口 元三, 鳴海 覚志, 高木 優樹, 石井 智弘, 長谷川 奉延, 六車 恵子, 小川 渉, 高橋 裕

    日本内分泌学会雑誌   Vol. 93 ( 1 ) page: 249 - 249   2017.4

     More details

    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher:(一社)日本内分泌学会  

▼display all

Presentations 200

  1. GPR101はヒトiPS細胞由来視床下部-下垂体オルガノイドの腹側視床下部領域に発現する

    森川俊太郎, 須賀英隆, 金子直哉, 菱村希, 中村明枝

    第97回日本内分泌学会学術総会  2024.6.6 

     More details

    Event date: 2024.6

    Language:Japanese   Presentation type:Poster presentation  

  2. 高用量のステロイド投与時にのみ多尿を呈する病態機序の解明

    栗本隼樹, 高木博史, 川口頌平, 宮田 崇, 萩原大輔, 岩間信太郎, 須賀英隆, 安藤史顕, 内田信一, 有馬 寛

    第97回日本内分泌学会学術総会  2024.6.6 

     More details

    Event date: 2024.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  3. 下垂体発生における視床下部-口腔外胚葉組織間作用の多面的役割

    松本隆作, 須賀英隆, 山本拓也

    第97回日本内分泌学会学術総会  2024.6.6 

     More details

    Event date: 2024.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  4. ラット胚性幹細胞を用いた弓状核キスペプチンニューロン分化誘導法の検討

    長谷川咲希, 須賀英隆, 三宅菜月, 大須賀智子, 平林真澄, 井上直子, 上野山賀久, 束村博子, 有馬寛

    第97回日本内分泌学会学術総会  2024.6.6 

     More details

    Event date: 2024.6

    Language:Japanese   Presentation type:Oral presentation (general)  

  5. ヒトiPS細胞を用いたACTH産生腫瘍モデル

    松本隆作, 荒木貴子, 須賀英隆, 山本拓也

    第97回日本内分泌学会学術総会  2024.6.7 

     More details

    Event date: 2024.6

    Language:Japanese   Presentation type:Poster presentation  

  6. Revolutionizing treatment: cell-based solution for hypopituitarism. Invited

    Suga H, Taga S, Arima H

    2024.4.12 

     More details

    Event date: 2024.4

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  7. 視床下部-下垂体系オルガノイド

    須賀英隆、松本隆作、尾崎創、三輪田勤、有馬寛

    第101回生理学会大会  2024.3.30  日本生理学会

     More details

    Event date: 2024.3

    Language:Japanese  

    Venue:小倉(北九州市)  

  8. 視床下部-下垂体系オルガノイド

    須賀英隆, 松本隆作, 尾崎創, 三輪田勤, 有馬寛

    第101回生理学会大会  2024.3.30 

     More details

    Event date: 2024.3

    Language:English   Presentation type:Oral presentation (general)  

  9. 受精卵ゲノム編集を応用した副腎欠損マウスの短期間作製法

    加納麻弓子, 水谷英二, 長坂智裕, 須賀英隆, 曽根正勝

    第31回日本ステロイドホルモン学会学術集会  2024.3.9 

     More details

    Event date: 2024.3

    Language:English   Presentation type:Oral presentation (general)  

  10. ヒト下垂体製剤の皮下移植

    近藤辰磨, 須賀英隆, 多賀詩織, 佐々木博勇, 原田英幸, 永田雄一, 竹内和人, 伊藤英治, 有馬寛, 齋藤竜太

    第34回日本間脳下垂体腫瘍学会  2024.2.16 

     More details

    Event date: 2024.2

    Language:English   Presentation type:Oral presentation (general)  

  11. 下垂体の発生 Invited

    須賀英隆

    第34回日本間脳下垂体腫瘍学会  2024.2.17 

     More details

    Event date: 2024.2

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  12. 視床下部-下垂体オルガノイドによる発生/再生/病態研究

    須賀英隆, 松本隆作, 多賀詩織, 加納麻弓子, 尾崎 創, 三輪田 勤, 有馬 寛

    第46回日本分子生物学会年会  2023.12.8 

     More details

    Event date: 2023.12

    Language:English   Presentation type:Symposium, workshop panel (public)  

  13. 視床下部オルガノイドを用いたこれまでの研究と博士研究員である現在、今後の展望 ~若手研究者の立場から~

    三輪田勤, 坂口秀哉, 須賀英隆, 有馬寛

    第49回日本神経内分泌学会学術集会  2023.10.27 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  14. Deep Learning を利用した多能性幹細胞の分化予測

    淺野友良, 須賀英隆, 村上 奏, 湯川 博, 新岡宏彦, 有馬 寛

    第49回日本神経内分泌学会学術集会  2023.10.27 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  15. Gonadotroph PitNET におけるoncocytic changeの特徴

    須賀 英隆, 井下 尚子, 山田 正三, 有馬 寛

    第49回日本神経内分泌学会学術集会  2023.10.28 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  16. ヒト多能性幹細胞由来視床下部・下垂体オルガノイドに存在する 下垂体幹 / 前駆細胞の分離法

    河田美穂, 小谷 侑, 亀山俊樹, 齋藤加奈子, 須賀英隆, 長崎 弘

    第49回日本神経内分泌学会学術集会  2023.10.28 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  17. 弓状核キスぺプチンニューロンの発生制御メカニズム解明に向けた ラット胎仔脳における視床下部マーカー発現の検討

    長谷川咲希, 須賀英隆, 三宅菜月, 大須賀智子, 井上直子, 上野山賀久, 束村博子, 有馬 寛

    第49回日本神経内分泌学会学術集会  2023.10.28 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  18. 視床下部→下垂体茎→下垂体における各ホルモンの免疫染色

    井下尚子, 田邊宣昭, 須賀英隆, 神田浩明

    第49回日本神経内分泌学会学術集会  2023.10.27 

     More details

    Event date: 2023.10

    Language:English   Presentation type:Oral presentation (general)  

  19. 視床下部におけるASK3の発現~視床下部ホルモンとの関係~

    井下尚子, 須賀英隆, 名黒功, 神田浩明

    第27回日本臨床内分泌病理学会学術総会  2023.9.22 

     More details

    Event date: 2023.9

    Language:English   Presentation type:Oral presentation (general)  

  20. マウス疾患特異的iPS細胞を利用してケミカルシャペロンの治療効果を簡便に評価する

    須賀英隆, 三輪田勤, 有馬寛

    第41回 内分泌代謝学サマーセミナー  2023.7.7 

     More details

    Event date: 2023.7

    Language:English   Presentation type:Poster presentation  

  21. 動物体内環境を利用した副腎の再生

    加納麻弓子, 水谷英二, 須賀英隆, 曽根正勝

    第41回 内分泌代謝学サマーセミナー  2023.7.7 

     More details

    Event date: 2023.7

    Language:Japanese   Presentation type:Poster presentation  

  22. ヒトiPS細胞由来オルガノイドを用いた視床下部-下垂体系発生におけるLHX4の機能解析

    松本隆作, 須賀英隆, 高橋 裕, 山本拓也

    第41回内分泌代謝学サマーセミナー  2023.7.7 

     More details

    Event date: 2023.7

    Language:English   Presentation type:Poster presentation  

  23. ステロイド使用中に診断された中枢性尿崩症の一例

    淺野友良, 須賀英隆, 石黒文菜, 栗本隼樹, 尾上剛史, 有馬寛

    日本内科学会第250回東海地方会  2023.6.25 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  24. CRISPR-Cas9を用いた高効率な副腎欠損マウス作出

    加納麻弓子, 水谷英ニ, 須賀英隆, 及川律子, 曽根正勝

    第96回 日本内分泌学会学術総会  2023.6.1 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  25. ヒトES細胞由来下垂体細胞のマウス皮下移植の有効性

    佐々木博勇, 須賀英隆, 竹内和人, 永田雄一, 原田英幸, 近藤辰磨, 伊藤英治, 有馬寛, 齋藤竜太

    第96回日本内分泌学会学術総会  2023.6.2 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  26. 再生医療実現のためのヒト下垂体組織の新規製法開発

    多賀詩織, 中野徳重, 桑原篤, 須賀英隆, 有馬寛

    第96回日本内分泌学会学術総会  2023.6.1 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  27. 下垂体再生医療への到達点 Invited

    須賀英隆, 有馬寛

    第96回日本内分泌学会学術総会  2023.6.3 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  28. マウスES細胞からの視床下部キスペプチンニューロンの分化誘導法の検討

    三宅菜月, 須賀 英隆, 大須賀智子, 関 友望, 井上直子, 上野山賀久, 小谷友美, 梶山広明, 束村博子, 有馬寛

    第96回日本内分泌学会学術総会  2023.6.1 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  29. in vitro創出したヒト視床下部神経幹細胞の性質検討

    三輪田勤, 須賀英隆, 有馬寛

    第96回日本内分泌学会学術総会  2023.6.1 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Poster presentation  

  30. DeepLearningによるヒトES細胞培養過程の予測

    淺野友良, 須賀英隆, 筒井奎剛, 村上奏, 湯川博, 新岡宏彦, 有馬寛

    第96回日本内分泌学会学術総会  2023.6.2 

     More details

    Event date: 2023.6

    Language:English   Presentation type:Oral presentation (general)  

  31. iPS細胞を用いた内分泌系の臓器再生 Invited

    須賀英隆

    第31回日本医学会総会 シンポジウム柱2 革新的医療技術の最前線 「臓器代替技術の現状と新展開」  2023.4.22 

     More details

    Event date: 2023.4

    Language:English   Presentation type:Oral presentation (general)  

  32. ヒト多能性幹細胞から分化誘導した脳下垂体細胞の成熟方法

    須賀英隆, 多賀詩織, 中野徳重, 桑原篤, 松本隆作, 加納麻弓子, 三輪田勤, 有馬寛

    第22回日本再生医療学会  2023.3.24 

     More details

    Event date: 2023.3

    Language:English   Presentation type:Oral presentation (general)  

  33. 視床下部・下垂体の再生医療とその先 Invited

    須賀英隆, 有馬寛

    第33回日本間脳下垂体腫瘍学会  2023.3.4 

     More details

    Event date: 2023.3

    Language:English   Presentation type:Oral presentation (general)  

  34. ヒト視床下部・下垂体オルガノイドから分離した接着性細胞の下垂体肝細胞性の検討、

    野々山葵, 河田美穂, 小谷 侑, 亀山俊樹, 齋藤加奈子, 須賀英隆, 長崎 弘

    第48回日本神経内分泌学会学術集会  2022.10.30 

     More details

    Event date: 2022.10

    Language:Japanese   Presentation type:Oral presentation (general)  

  35. 下垂体の再生研究 Invited

    須賀英隆, 松本隆作, 有馬寛

    第26回日本内分泌病理学会学術総会  2022.10.29 

     More details

    Event date: 2022.10

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  36. ヒト多能性幹細胞からの機能的な視床下部-下垂体ユニット作製 Invited

    須賀 英隆, 有馬 寛

    第165回日本獣医学会学術集会  2022.9.7 

     More details

    Event date: 2022.9

    Language:English   Presentation type:Oral presentation (general)  

  37. ヒト多能性幹細胞からの下垂体幹/前駆細胞培養の樹立について

    野々山葵, 河田美穂, 小谷 侑, 亀山俊樹, 齋藤加奈子, 須賀英隆, 長崎 弘

    第36回日本下垂体研究会学術集会  2022.8.10 

     More details

    Event date: 2022.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東海大学山中湖セミナーハウス  

  38. DeepLearningによるヒトES細胞培養過程の予測

    淺野 友良, 筒井, 奎剛, 須賀 英隆, 新岡 宏彦, 湯川 博, 有馬 寛

    第40回内分泌代謝学サマーセミナー  2022.7.7 

     More details

    Event date: 2022.7

    Language:English   Presentation type:Oral presentation (general)  

  39. ヒト多能性幹細胞由来の視床下部・下垂体オルガノイドにおける下垂体幹/前駆細胞の探索

    野々山葵, 河田美穂, 小谷 侑, 亀山俊樹, 齋藤加奈子, 須賀英隆, 長崎 弘

    Neuro 2022(日本神経科学学会、日本神経化学会、日本神経回路学会合同大会) 

     More details

    Event date: 2022.6 - 2022.7

    Language:English   Presentation type:Poster presentation  

  40. Making hypothalamatic-pituitary organoids in a dish. Invited

    Hidetaka Suga

    Yogesh C. Patel Memorial Lecture, McGill University Endocrinology Research and Education Day  2022.5.26  c

     More details

    Event date: 2022.5

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:McGill University   Country:Canada  

  41. 下垂体の再生 Invited

    須賀英隆, 有馬寛

    第32回日本間脳下垂体腫瘍学会  2022.2.18 

     More details

    Event date: 2022.2

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  42. ヒト疾患特異的人工多能性幹細胞(iPS細胞)からのバソプレシン(AVP)神経の分化誘導による家族性中枢性尿崩症(FNDI)のin vitroヒト疾患モデル

    尾崎創, 須賀英隆, 三輪田勤, 井口元三, 高橋裕, 有馬寛

    第47回日本神経内分泌学会学術集会  2021.10.30 

     More details

    Event date: 2021.10

    Language:English   Presentation type:Oral presentation (general)  

  43. 多能性幹細胞を用いた神経内分泌器官作出と機能解析 Invited

    加納麻弓子, 水野直彬, 水谷英二, 須賀英隆, 有馬寛, 中内啓光

    第47回日本神経内分泌学会学術集会  2021.10.30 

     More details

    Event date: 2021.10

    Language:English   Presentation type:Oral presentation (general)  

  44. Regeneration of Parethyroid Glands that Function in Response to Calcium. Invited

    Kano M, Mizuno N, Mizutani E, Suga H, Arima H

    the 9th Seoul International Congress of Endocrinology and Metabolism in conjunction with the 40th Annual Scientific Meeting of Korean Endocrine Society (SICEM 2021)  2021.10.29 

     More details

    Event date: 2021.10

    Language:English   Presentation type:Oral presentation (general)  

  45. 試験管内で作る視床下部・下垂体 Invited

    須賀英隆, 有馬寛

    第22回日本内分泌学会関東甲信越支部学術集会・総会  2021.9.24 

     More details

    Event date: 2021.9

    Language:English   Presentation type:Oral presentation (general)  

  46. iPS 細胞を用いた革新的下垂体疾患モデルの作成と病因・病態解析 Invited

    高橋 裕, 松本隆作, 蟹江慶太郎, 伊藤 剛, 金子 新, 須賀英隆, 福岡秀規, 井口元三

    第35回日本下垂体研究会学術集会  2021.8.21 

     More details

    Event date: 2021.8

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  47. 視床下部-下垂体系の再生医療 Invited

    須賀英隆, 有馬 寛

    第35回日本下垂体研究会学術集会  2021.8.21 

     More details

    Event date: 2021.8

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  48. ナイーブ化による家族性中枢性尿崩症(FNDI)ヒト疾患特異的iPS細胞からのパソプレシン(AVP)ニューロンの分化誘導

    尾崎創, 須賀英隆, 三輪田勤, 有馬寛

    第39回日本内分泌学会 内分泌代謝学サマーセミナー  2021.7.9 

     More details

    Event date: 2021.7

    Language:Japanese   Presentation type:Poster presentation  

  49. ヒトiPS細胞を用いた下垂体発生・疾患研究

    松本隆作, 須賀英隆, 高橋裕, 山本拓也

    第39回日本内分泌学会 内分泌代謝学サマーセミナー  2021.7.9 

     More details

    Event date: 2021.7

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  50. ヒトES細胞を用いてタニサイト様細胞への分化誘導を試みる

    三輪田勤, 須賀英隆, 尾崎創, 有馬寛

    第39回日本内分泌学会 内分泌代謝学サマーセミナー  2021.7.9 

     More details

    Event date: 2021.7

    Language:Japanese   Presentation type:Poster presentation  

  51. カルシウム応答性を有する機能的な副甲状腺再生

    加納麻弓子, 水野直彬, 水谷英二, 正木英樹, 須賀英隆, 中内啓光

    第94回日本内分泌学会学術総会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  52. 試験管内で再現する視床下部‐下垂体オルガノイド Invited

    須賀英隆, 有馬寛

    第94回日本内分泌学会学術総会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  53. 視床下部・下垂体の再生医学 Invited

    笠井貴敏, 須賀英隆, 有馬寛

    第110回日本病理学会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  54. 機械学習を用いた下垂体オルガノイド分化効率予測モデルの作成

    松本 隆作, 須賀 英隆, 青井 貴之, 高橋 裕, 山本 拓也

    第94回日本内分泌学会学術総会  2021.4.23 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  55. 家族性中枢性尿崩症(FNDI)ヒトiPS細胞からのバソプレシン(AVP)ニューロンの分化誘導

    尾崎創, 三輪田勤, 光本一樹, 須賀英隆, 有馬寛

    第94回日本内分泌学会学術総会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Poster presentation  

  56. マウスES細胞を用いたキスペプチンニューロンを含む視床下部弓状核の分化誘導法の検討

    三宅菜月, 須賀英隆, 大須賀智子, 井上直子, 上野山賀久, 小谷友美, 梶山広明, 束村博子, 有馬寛

    第94回日本内分泌学会学術総会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Poster presentation  

  57. バソプレシンニューロンにおいて異常タンパク凝集体は小胞体から輸送隔離されることなく小胞体内部で分解される―家族性中枢性尿崩症モデルマウスを用いた検討―

    宮田崇, 萩原大輔, 津村哲郎, 蓬臺優一, 川口頌平, 栗本隼樹, 髙木博史, 須賀英隆, 川上奈津子, 坂本浩隆, 松本真実, 大野伸彦, 有馬寛

    第94回日本内分泌学会学術総会  2021.4.22 

     More details

    Event date: 2021.4

    Language:Japanese   Presentation type:Oral presentation (general)  

  58. 視床下部-下垂体系の機能的連携 Invited

    須賀英隆, 松本隆作, 笠井貴敏, 有馬寛

    第20回日本再生医療学会総会  2021.3.11 

     More details

    Event date: 2021.3

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  59. 視床下部・下垂体の再生医療 Invited

    須賀英隆, 尾崎創, 三輪田勤, 三宅菜月, 加納麻弓子, 多賀詩織, 桑原篤, 木村徹, 中野徳重, 小林久美子, 北本幸子, 有馬寛

    第20回日本再生医療学会総会  2021.3.13 

     More details

    Event date: 2021.3

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  60. Toward the regenerative medicine for hypothalamic and pituitary disorders using pluripotent stem cells. Invited

    Hidetaka Suga, Hiroshi Arima

    The 19th International Congress of Endocrinology (ICE Virtual 2021)  2021.2.26 

     More details

    Event date: 2021.2

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  61. Making a Pituitary Gland in a Dish. Invited

    Hidetaka Suga, Hiroshi Arima

    The 17th Asia-Oceania Congress of Endocrinology and the 8th Seoul International Congress of Endocrinology and Metabolism (AOCE-SICEM 2020)  2020.10.28 

     More details

    Event date: 2020.10

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  62. iPS細胞を利用した糖尿病・内分泌疾患研究 Invited

    須賀英隆

    第8回名古屋大学糖尿病医療連携フォーラム 

     More details

    Event date: 2019.12

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  63. Towards the Regenerative Medicine for Pituitary Using iPS Cells. Invited

    Hidetaka Suga

    The 8th Pituitary Experts Meeting in Asia (PEMA)  2019.11.22 

     More details

    Event date: 2019.11

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  64. ヒト多能性幹細胞を用いた視床下部・下垂体研究 Invited International conference

    須賀英隆

    第4回NLS(ナノライフシステム)セミナー 

     More details

    Event date: 2019.11

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  65. iPS細胞を利用した視床下部‐下垂体の医療

    須賀英隆

    あいちサイエンスフェスティバルサイエンストーク 

     More details

    Event date: 2019.10

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

    Country:Japan  

  66. ES/iPS細胞を用いた視床下部・下垂体再生医療と病理への展開

    須賀英隆,松本隆作,有馬寛

    第23回日本臨床内分泌病理学会学術総会 

     More details

    Event date: 2019.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  67. 疾患特異的iPS細胞を利用した視床下部・下垂体難病研究 Invited

    須賀英隆

    中部幹細胞クラブシンポジウム2019「幹細胞人類学 幹細胞でヒトの発生・生理・疾患・進化を理解する」 

     More details

    Event date: 2019.9

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  68. ヒト多能性幹細胞由来3次元培養視床下部/下垂体組織の形態学的検討 第1報

    井下尚子,須賀英隆

    第34回下垂体研究会学術集会 

     More details

    Event date: 2019.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  69. マウスES細胞から分化誘導した視床下部神経幹細胞

    須賀英隆,加納麻弓子,有馬寛

    第34回下垂体研究会学術集会 

     More details

    Event date: 2019.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  70. ヒトiPS細胞から下垂体PRL産生細胞への分化誘導

    永井孝,須賀英隆,大須賀智子,有馬寛

    第92回日本内分泌学会学術総会 

     More details

    Event date: 2019.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  71. 下垂体発生における視床下部-口腔外胚葉間FGFの役割

    松本隆作,青井貴之,小柳三千代,須賀英隆,福岡秀規,井口元三,小川渉,高橋

    第92回日本内分泌学会学術総会 

     More details

    Event date: 2019.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  72. 家族性中枢性尿崩症疾患特異的iPS細胞を用いた4-PBAによる治療の可能性

    光本一樹,須賀英隆,有馬寛

    第92回日本内分泌学会学術総会 

     More details

    Event date: 2019.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  73. 視床下部・下垂体疾患に対する再生医療 Invited International conference

    須賀英隆, 有馬寛

    第18回日本再生医療学会総会 

     More details

    Event date: 2019.3

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  74. 間脳下垂体における再生医療 Invited International conference

    須賀英隆

    第29回日本間脳下垂体腫瘍学会 

     More details

    Event date: 2019.2

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  75. 下垂体の再生医療

    須賀英隆

    厚生労働科学研究費補助金難治性疾患等政策研究事業 (難治性疾患政策研究事業)間脳下垂体機能障害に関する調査研究班 市民公開講座 

     More details

    Event date: 2019.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  76. マウスES細胞視床下部分化誘導系後期に残存するRax+細胞はTanycytesと類似する

    加納麻弓子, 須賀英隆, 有馬寛

    名古屋大学医学系研究科・創薬科学研究科・環境医学研究所三部局交流シンポジウム  2018.11.30 

     More details

    Event date: 2018.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  77. 小胞体ストレスのin vitro実験系の確立~家族性中枢性尿崩症の疾患特異的iPS細胞を用いた検討~

    光本一樹, 須賀英隆, 坂本浩隆, 有馬寛

    名古屋大学医学系研究科・創薬科学研究科・環境医学研究所三部局交流シンポジウム  2018.11.30 

     More details

    Event date: 2018.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  78. マウスES細胞視床下部分化誘導系後期に残存するRax<SUP>+</SUP>細胞はTanycytesと類似する

    加納麻弓子, 須賀英隆, 有馬寛

    第45回日本神経内分泌学会学術集会  2018.10.27 

     More details

    Event date: 2018.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  79. マウス ES 細胞視床下部分化誘導系における Tanycytes 様細胞

    加納麻弓子, 須賀英隆, 有馬寛

    第8回生理研・名大医合同シンポジウム  2018.9.29 

     More details

    Event date: 2018.9

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  80. Functional hypothalamus and pituitary induction in vitro from human pluripotent stem cells. Invited International conference

    Hidetaka Suga, Chikafumi Ozone, Koichiro Ogawa, Takatoshi Kasai, Kazuki Mistsumoto, Hiroshi Arima

    5th Tissue Engineering and Regenerative Medicine International Society World Congress (TERMIS 2018)  2018.9 

     More details

    Event date: 2018.9

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  81. 試験管内で再現する下垂体発生 Invited

    須賀英隆, 有馬寛

    第33回日本下垂体研究会学術集会  2018.8.19 

     More details

    Event date: 2018.8

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  82. マウスES細胞視床下部誘導系後期に残存するRax陽性細胞は腹側Tanycytesと類似する

    加納麻弓子, 須賀英隆, 有馬寛

    第36回内分泌代謝学サマーセミナー  2018.8.2 

     More details

    Event date: 2018.8

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  83. 下垂体の再生医療に向けて Invited

    須賀 英隆

    第6回下垂体スキルアップカンファレンス  2018.7.28 

     More details

    Event date: 2018.7

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  84. Allo and hetero-graft survival of Hypothalamic Neuron from Mouse Embryonic Stem Cell

    Hidetaka Suga

    Allo and hetero-graft survival of Hypothalamic Neuron from Mouse Embryonic Stem Cell  2018.7.26 

     More details

    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  85. マウスES細胞由来-視床下部組織におけるMCHニューロンの組織学的および神経化学的特徴

    小谷侑, 須賀英隆, 金子葉子, 中島昭, 長崎弘

    第41回日本神経科学大会  2018.7.26 

     More details

    Event date: 2018.7

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  86. 多能性幹細胞の極性発現のための濃度勾配培養チャンバーの開発

    須賀英隆, 杉浦慎治, 長崎玲子, 田村磨聖, 佐藤琢, 長崎晃, 金森敏幸

    化学とマイクロ・ナノシステム学会第37回研究会  2018.5.22 

     More details

    Event date: 2018.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  87. 転写因子OTX2は視床下部からのFGFシグナルを介して下垂体を分化させる

    松本 隆作, 須賀 英隆, 井口 元三, 福岡 秀規, 長谷川 奉延, 六車 恵子, 小川 渉, 青井 貴之, 高橋 裕

    第91回日本内分泌学会学術総会  2018.4.26 

     More details

    Event date: 2018.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  88. マウスES細胞視床下部誘導系におけるTanycytes様細胞の検討

    加納麻弓子, 須賀英隆, 山田登美子, 有馬寛

    第91回日本内分泌学会学術総会  2018.4.26 

     More details

    Event date: 2018.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  89. マウス胚性幹細胞由来バゾプレシン神経の解析

    金子葉子, 大熊真人, 小谷 侑, 須賀英隆, 中島 昭, 宮地栄一, 長崎 弘

    第95回日本生理学会大会  2018.3.28 

     More details

    Event date: 2018.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  90. 視床下部・下垂体の再生医療および病態研究 Invited

    須賀 英隆

    第1回若手下垂体医師の会  2018.3.24 

     More details

    Event date: 2018.3

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  91. マウスES細胞由来視床下部神経の同種移植

    長崎 弘, 小谷 侑, 須賀 英隆, 金子 葉子

    第28回バゾプレシン研究会学術集会  2018.1.6 

     More details

    Event date: 2018.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  92. 家族性中枢性尿崩症の疾患特異的iPS細胞を用いた小胞体ストレスの再現

    光本一樹, 須賀英隆, 加納麻弓子, 大曾根親文, 宮田崇, 橡谷昌佳, 萩原大輔, 佐藤彗太, 坂本浩隆, 有馬寛, 大磯ユタカ

    第28回バゾプレシン研究会  2018.1.6 

     More details

    Event date: 2018.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  93. ES細胞・iPS細胞を用いた再生医療最前線 Invited

    須賀 英隆

    「国民との科学技術対話」に基づくアウトリーチ活動  2017.12.22 

     More details

    Event date: 2017.12

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  94. 疾患特異的iPS細胞を用いたLHX4異常症の発症機序の解明

    松本 隆作, 須賀 英隆, 青井 貴之, 高木 優樹, 長谷川 奉延, 六車 恵子, 小川 渉, 高橋 裕

    第27回臨床内分泌代謝Update  2017.11.24 

     More details

    Event date: 2017.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  95. in vitro下垂体分化法を生体により近づける試み

    須賀英隆

    第44回日本神経内分泌学会学術集会 

     More details

    Event date: 2017.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  96. 下垂体分化における視床下部隣接の意義

    須賀 英隆, 笠井 貴敏, 有馬 寛

    第32回日本下垂体研究会学術集会 

     More details

    Event date: 2017.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  97. 視床下部・下垂体の再生医療および病態研究

    須賀英隆

    京都大学ウイルス・再生医科学研究所セミナー 

     More details

    Event date: 2017.7

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  98. 4-PBA は家族性中枢性尿崩症の小胞体ストレスを軽減する-モデルマウスを用いた検討

    橡谷昌佳, 萩原大輔, 宮田 崇, 森下啓明, 光本一樹, 須賀英隆, 有馬 寛

    第27回バゾプレシン研究会  2017.1.7 

     More details

    Event date: 2017.1

    Language:Japanese   Presentation type:Oral presentation (general)  

  99. Recapitulating hypothalamus and pituitary development using ES/iPS cells. International conference

    Hidetaka Suga

    Stem Cells in Neuroendocrinology. 

     More details

    Event date: 2015.12

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:France  

  100. SNAP25と相互作用する128kDa蛋白の同定と、ES-AVP培養系を用いたバゾプレシン分泌における機能解析

    竹内誠治,椙村益久,岩田尚子,中島孝太郎,泉田久和,藤沢治樹,高木博史,岩間信太郎,須賀英隆,有馬寛,大磯ユタカ

    第88回日本内分泌学会学術総会 

     More details

    Event date: 2015.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  101. マウス胚性幹細胞由来バゾプレシン細胞のライブイメージング

    須藤湧太,長崎弘,小谷侑,山本直樹,須賀英隆,金子葉子,中島昭,太田明

    第88回日本内分泌学会学術総会 

     More details

    Event date: 2015.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  102. マウスES細胞由来-視床下部培養系におけるNERP1の作用

    長崎弘,須藤湧太,小谷侑,須賀英隆,山本直樹,金子葉子,中島昭,太田明

    第88回日本内分泌学会学術総会 

     More details

    Event date: 2015.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  103. Calcium imaging of vasopressin neuron in the hypothalamic culture derived from mouse embryonic stem cell.

    Hiroshi Nagasaki, Yu Kodani, Naoki Yamamoto, Hidetaka Suga, Yoko Kaneko, Akira Nakashima, Akira Ota

     More details

    Event date: 2015.3

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  104. Influence of endogenous Akt/β-catenin signaling in hypothalamic differentiation from mouse embryonic stem cells

    Yu Kodani, Hiroshi Nagasaki, Hidetaka Suga,Yoko S, Kaneko, Akira Nakashima, Akira Ota

     More details

    Event date: 2015.3

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  105. Making an Anterior Pituitary from human ES/iPS cells in a Dish

    Hidetaka Suga

     More details

    Event date: 2015.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  106. マウス胚性幹細胞由来バゾプレシン細胞のライブイメージング

    長崎弘,小谷侑,須賀英隆,山本直樹,金子葉子,中島昭,太田明

    第25回バゾプレシン研究会 

     More details

    Event date: 2015.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  107. 多能性幹細胞を用いた視床下部・下垂体研究

    須賀英隆,大磯ユタカ,水野正明

    第24回臨床内分泌代謝Update 

     More details

    Event date: 2014.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  108. ヒトES細胞を用いた機能的な下垂体前葉細胞の分化方法確立

    須賀英隆,大曽根親文,水野正明,大磯ユタカ

    第4回生理学研究所・名古屋大学 合同シンポジウム 

     More details

    Event date: 2014.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  109. ヒトES細胞からバソプレシン産生細胞への分化誘導

    小川晃一郎,須賀英隆,水野正明,大磯ユタカ

    第4回生理学研究所・名古屋大学 合同シンポジウム 

     More details

    Event date: 2014.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  110. Differentiation into hypothalamic and pituitary cells from pluripotent stem cells International conference

    Hidetaka Suga

    The International Congress of Neuroendocrinology 2014 

     More details

    Event date: 2014.8

    Language:English   Presentation type:Oral presentation (invited, special)  

    Country:Australia  

  111. 多能性幹細胞を用いた、視床下部・下垂体の分化

    須賀英隆,落合啓史,大曽根親文,大磯ユタカ,水野正明

    第29回日本下垂体研究会学術集会 

     More details

    Event date: 2014.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  112. BMP4シグナルはマウスES細胞の口腔外胚葉への分化誘導の安定化に寄与する

    落合啓史, 大磯ユタカ, 有馬寛, 椙村益久, 須賀英隆, 小川晃一郎

    第29回日本下垂体研究会学術集会 

     More details

    Event date: 2014.8

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  113. ES細胞由来-視床下部培養系におけるMCHニューロンの特徴

    長崎弘,小谷侑,須賀 英隆, 金子葉子,中島昭,太田明

    第87回日本内分泌学会学術総会 

     More details

    Event date: 2014.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  114. 慢性低ナトリウム環境において、ミクログリアは過剰な活性化へとプライムされ、浸透圧性脱髄症候群の病態形成に関与する.

    高木博史, 椙村益久, 鈴木陽之, 泉田久和, 藤沢治樹, 中島孝太郎, 小川晃一郎, 竹内誠治, 落合啓史, 岩間信太郎, 須賀 英隆, 土井由紀子, 川ノ口潤, 竹内英之, 水野哲也,有馬寛,錫村明生,大磯ユタカ

    第87回日本内分泌学会学術総会 

     More details

    Event date: 2014.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  115. マウスES細胞から視床下部・下垂体への分化とその応用

    須賀英隆,大磯ユタカ,水野正明

    第13回日本再生医療学会総会 

     More details

    Event date: 2014.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  116. Minocycline prevents osmotic demyelination associated with aquaresis

    Hiroshi Takagi, Yoshihisa Sugimura, Hisakazu Izumida, Haruki Fujisawa, Kohtaroh Nakashima, Koichiro Ogawa, Seiji Takeuchi, Hiroshi Ochiai, Atsushi Kiyota, Shintaro Iwama, Hidetaka Suga, Hiroshi Arima,Yutaka Oiso.

     More details

    Event date: 2014.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  117. Differentiation into rostral hypothalamic precursor from human pluripotent stem cells in 3D culture.

    Koichiro Ogawa, Hidetaka Suga

     More details

    Event date: 2014.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  118. BMP4 signal treatment differentiates the mouse embryonic stem cells into the oral ectoderm.

    Hiroshi Ochiai, Hidetaka Suga

     More details

    Event date: 2014.2

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  119. 水利尿を介した血清ナトリウム濃度上昇に伴う浸透圧性脱髄症候群の病態解析

    髙木博史,椙村益久,鈴木陽之,泉田久和,藤沢治樹, 小川晃一郎,中島孝太郎,落合啓史,竹内誠治,岩間信太郎,須賀英隆,有馬寛,大磯ユタカ

    第24回バゾプレシン研究会 

     More details

    Event date: 2014.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  120. マウスES細胞から視床下部・下垂体への分化と、ヒト細胞への応用.

    須賀英隆,大磯ユタカ,水野正明

    日本人類遺伝学会第58回大会 

     More details

    Event date: 2013.11

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  121. マウスES細胞由来視床下部誘導系におけるバゾプレシン細胞の解析

    長崎弘,福岡一貴,小谷侑,須賀英隆,笹井芳樹,金子葉子,中島顕,大磯ユタカ,太田明

    第59回中部日本生理学会 

     More details

    Event date: 2013.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  122. マウスESC由来視床下部細胞のラット脳移植

    長崎弘,小谷侑,金子葉子,中島昭,須賀英隆,太田明

    第59回中部日本生理学会 

     More details

    Event date: 2013.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  123. Overly rapid correction of severe hyponatremia with vasopressin receptor antagonists poses a risk of inducing osmotic demyelination syndrome and hemorrhage. International conference

    Hiroshi Takagi, Yoshihisa Sugimura, Hisakazu Izumida, Haruki Fujisawa, Nakashima, Ogawa,Seiji Takeuchi, Hiroshi Ochiai, Atsushi Kiyota, Hidetaka Suga, Yutaka Oiso.

    Neuroscience 2013 

     More details

    Event date: 2013.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  124. Chronic hyponatremia causes gait disturbance in rats. International conference

    H Fujisawa, Y Sugimura, H Mizoguchi, H Takagi, H Izumida, K Nakashima, K Ogawa, S Takeuchi, H Ochiai, A Kiyota, H Suga, H Takeuchi, Y Murata, Y Oiso.

    Neuroscience 2013 

     More details

    Event date: 2013.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  125. 高用量のバゾプレシン受容体拮抗薬による血清Naの急激な上昇は浸透圧性脱髄症候群や頭 蓋内出血を惹起する危険性がある.

    高木博史,椙村益久,泉田久和,藤沢治樹,中島孝太郎,小川晃一郎,竹内誠治,落合啓史,清田篤志,須賀英隆,有馬寛,大磯ユタカ

    第40回日本神経内分泌学会学術集会 

     More details

    Event date: 2013.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  126. マウスES細胞から視床下部・下垂体への分化と、ヒト細胞への応用.

    須賀英隆

    第40回日本神経内分泌学会学術集会 

     More details

    Event date: 2013.10

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  127. ES細胞由来AVP細胞培養系におけるRab3a、Rabphilin3a、SNAP25のAVP分泌への関与

    清田篤志,椙村益久,竹内誠治,中島孝太郎,小川晃一郎,泉田久和,落合啓史,藤沢治樹,高木博史,須賀英隆,渡辺崇,長崎弘,有馬寛,大磯ユタカ

    第40回日本神経内分泌学会学術集会 

     More details

    Event date: 2013.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  128. 慢性低ナトリウム血症はラットにおいて歩行障害を惹起する

    藤沢治樹,椙村益久,溝口博之,高木博史,泉田久和,中島孝太郎,小川晃一郎,竹内誠治,落合啓史,清田篤志,須賀英隆,竹内英之,有馬寛,村田善晴,大磯ユタカ

    第40回日本神経内分泌学会学術集会 

     More details

    Event date: 2013.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  129. マウスES細胞から視床下部-下垂体への分化誘導

    須賀英隆,大曽根親文,落合啓史,大磯ユタカ

    第31回内分泌サマーセミナー 

     More details

    Event date: 2013.7

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  130. Involvement of Rab3a and Rabphilin3a in AVP secretion in ES cell-derived AVP neurons

    Atsushi Kiyota, Yoshihisa Sugimura, Seiji Takeuchi, Hisakazu Izumida, Hiroshi Ochiai, Haruki Fujisawa, Hiroshi Takagi, Kazuki Fukuoka, Hidetaka Suga, Takashi Watanabe, Hiroshi Nagasaki, Yutaka Oiso

     More details

    Event date: 2013.6

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  131. Overly rapid correction of hyponatremia with vasopressin antagonists poses a risk of inducing osmotic demyelination syndrome.

    Hiroshi Takagi, Yoshihisa Sugimura, Hisakazu Izumida, Haruki Fujisawa, Seiji Takeuchi, Hiroshi Ochiai, Atsushi Kiyota, Hidetaka Suga, Yutaka Oiso

     More details

    Event date: 2013.6

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  132. ES細胞由来-視床下部培養系におけるMCHニューロンの発生.

    小谷 侑,長崎 弘,須賀 英隆,綿谷 崇史,金子 葉子,中島 昭,大磯 ユタカ,笹井 芳樹,太田 明

    第36回日本神経科学大会 

     More details

    Event date: 2013.6

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  133. 劇症1型糖尿病を合併した薬剤性過敏症症候群の1例

    落合啓史,岡嵜裕子,尾方秀忠,須賀英隆,恒川新、大磯ユタカ

    第220回日本内科学会 東海地方会 

     More details

    Event date: 2013.6

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  134. ES細胞由来AVP産生細胞におけるRab関連タンパク質のAVP分泌への関与

    清田篤志,椙村益久,竹内誠治,泉田久和,落合啓史,藤沢治樹,高木博史,福岡一貴,須賀英隆,渡辺崇,長崎弘,有馬寛,大磯ユタカ

    第86回日本内分泌学会学術総会 

     More details

    Event date: 2013.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  135. 慢性低Na環境のミクログリアは過剰に活性化され浸透圧性脱髄症候群の病態に関与する

    高木博史,椙村益久,鈴木陽之,泉田久和,藤沢治樹,竹内誠治,落合啓史,清田篤志,須賀英隆,土井由紀子,川ノ口潤,竹内英之,水野哲也,有馬寛,錫村明生,大磯ユタカ

    第86回日本内分泌学会学術総会 

     More details

    Event date: 2013.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  136. ES細胞から分化誘導したAVP産生ニューロン培養系におけるRab3a関連蛋白のAVP分泌への関与の検討

    清田篤志, 椙村益久, 竹内誠治, 泉田久和, 落合啓史, 藤沢治樹, 高木博史, 福岡 一貴, 須賀英隆, 渡辺 崇, 長崎弘, 有馬寛, 大磯ユタカ

    第23回バゾプレシン研究会 

     More details

    Event date: 2013.1

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  137. リンパ球性漏斗下垂体後葉炎の診断検査薬の開発

    椙村益久, 岩間信太郎, 清田篤志, 竹内誠治, 泉田久和, 落合啓史, 藤沢治樹, 高木博史, 福岡 一貴, 須賀英隆, 長崎弘, 有馬寛, 大磯ユタカ

    間脳下垂体機能障害に関する調査研究班 平成24年度班会議 

     More details

    Event date: 2013.1

    Language:Japanese  

    Country:Japan  

  138. Endocrine cell generation by in vitro recapitulation of early pituitary development

    Hidetaka Suga

     More details

    Event date: 2012.10

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  139. マウスES細胞から下垂体への自己組織化誘導

    須賀英隆

     More details

    Event date: 2012.9

    Language:Japanese  

    Country:Japan  

  140. 下垂体ホルモン産生細胞を創る研究

    須賀英隆

    第1回KOBE内分泌・代謝スキルアップセミナー 

     More details

    Event date: 2012.9

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

    Country:Japan  

  141. 腎臓を創る-乗り越えるべき課題とその方策 ES細胞からの脳や内分泌組織の立体自己組織化

    須賀英隆

    日本腎臓学会学術総会 

     More details

    Event date: 2012.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  142. 再生医療と内分泌代謝疾患 ES細胞から下垂体への自己組織化誘導

    須賀英隆, 大磯ユタカ, 笹井芳樹

    第85回日本内分泌学会学術総会 

     More details

    Event date: 2012.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  143. マウスES細胞試験管内培養によるラトケ嚢形成とホルモン産生細胞への分化

    須賀英隆, 大磯ユタカ, 笹井芳樹

    第85回日本内分泌学会学術総会 

     More details

    Event date: 2012.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  144. マウスES細胞立体培養によるラトケ嚢形成とホルモン産生細胞への分化

    須賀英隆,大磯ユタカ,笹井芳樹

    間脳下垂体副腎研究会 

     More details

    Event date: 2012.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:東京   Country:Japan  

  145. マウスES細胞の3次元培養による機能的下垂体形成

    須賀英隆

    間脳下垂体腫瘍学会 

     More details

    Event date: 2012.2

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  146. 脂肪酸レセプター、GPR84の脂肪組織における発現についての検討.

    近藤貴昭, 長崎弘, 須賀英隆, 大磯ユタカ, 濱田洋司

    第53回日本糖尿病学会年次学術集会 

     More details

    Event date: 2010.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  147. Paclitaxelによる化学療法が有効であった甲状腺未分化癌の1例.

    深見亜也子, 稲垣朱実, 岡島由樹, 赤羽貴美子, 須賀英隆, 都築豊徳, 冨永芳博.

    第52回日本甲状腺学会 

     More details

    Event date: 2009.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  148. Novel treatment for nephrogenic diabetes insipidus rat model using the sendai-virus vector carrying aquaporin 2 gene. International conference

    Hidetaka Suga, Hiroshi Nagasaki, Taka-aki Kondo, Hiroshi Arima, Makoto Inoue, Mamoru Hasegawa, Yutaka Oiso.

    VIIIth World Congress on Neurohypophysial Hormones 

     More details

    Event date: 2009.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  149. Gene therapy for nephrogenic diabetes insipidus using pseudotyped simian immunodeficiency virus-based lentiviral vector carrying aquaporin 2 gene. International conference

    Taka-aki Kondo, Hiroshi Nagasaki, Hidetaka Suga, Makoto Inoue, Mamoru Hasegawa, Yutaka Oiso.

    VIIIth World Congress on Neurohypophysial Hormones 

     More details

    Event date: 2009.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  150. 第3世代サル免疫不全ウイルスシュードタイプベクターを用いた腎性尿崩症治療の開発.

    近藤貴昭, 長崎弘, 須賀英隆, 有馬寛, 井上誠, 長谷川護, 大磯ユタカ.

    第82回日本内分泌学会学術総会 

     More details

    Event date: 2009.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  151. Novel treatment for nephrogenic diabetes insipidus rat model using the sendai-virus vector carrying aquaporin 2 gene. International conference

    Hidetaka Suga, Hiroshi Nagasaki, Taka-aki Kondo, Hiroshi Arima, Yutaka Oiso.

    The Endocrine Society 2008 

     More details

    Event date: 2008.6

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  152. 遺伝性腎性尿崩症に対する遺伝子治療法の開発

    須賀英隆, 長崎弘, 近藤貴昭, 有馬寛, 大磯ユタカ

    第81回日本内分泌学会学術総会 

     More details

    Event date: 2008.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  153. 水代謝調節機構に関する新しい展開 腎性尿崩症に対する遺伝子治療法の開発.

    長崎弘, 須賀英隆, 近藤貴明, 大磯ユタカ

    第81回日本内分泌学会学術総会 

     More details

    Event date: 2008.5

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Country:Japan  

  154. 糖蛋白ホルモン、サイロスティムリンはヒト下垂体ACTH産生細胞に局在する.

    岡島由樹, 長崎弘, 長坂徹郎, 鈴木千津子, 須賀英隆, 永谷哲也, 須崎法幸, 齋藤清, 尾崎紀之, 大磯ユタカ

    日本甲状腺学会学術集会 

     More details

    Event date: 2007.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  155. 新規下垂体ホルモン、サイロスティムリンの転写調節機構.

    長崎弘, 岡島由樹, 鈴木千津子, 須賀英隆, 岩崎泰正, 大磯ユタカ

    日本甲状腺学会学術集会 

     More details

    Event date: 2007.11

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  156. 糖蛋白ホルモン、サイロスティムリンのヒト下垂体腫瘍における発現の検討.

    須賀英隆, 長崎弘, 岡島由樹, 長坂徹郎, 鈴木千津子, 永谷哲也, 須崎法幸, 齋藤清, 尾崎紀之, 大磯ユタカ

    日本甲状腺学会学術集会 

     More details

    Event date: 2007.11

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  157. The regulatory systems for novel pituitary hormone, thyrostimulin. International conference

    Hiroshi Nagasaki, Chizuko Suzuki, Yoshiki Okajima, Hidetaka Suga, Hiroshi Arima, Yutaka Oiso.

    Neuroscience 2007 

     More details

    Event date: 2007.11

    Language:English   Presentation type:Oral presentation (general)  

    Country:United States  

  158. A Novel Glycoprotein Hormone thyrostimulin Is Localized in the Corticotroph Cells of Human Anterior Pituitary. International conference

    Yoshiki Okajima, Hiroshi Nagasaki, Hidetaka Suga, Tetsuro Nagasaka, Noriyuki Ozaki, Kiyoshi Saito, Hiroshi Arima, Yutaka Oiso.

    Neuroscience 2007 

     More details

    Event date: 2007.11

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  159. 糖蛋白ホルモン、サイロスティムリンはヒト下垂体ACTH産生細胞に局在する.

    岡島由樹, 長崎弘, 長坂徹郎, 鈴木千津子, 須賀英隆, 永谷哲也, 須崎法幸, 齋藤清, 尾崎紀之, 大磯ユタカ

    第80回日本内分泌学会学術総会 

     More details

    Event date: 2007.6

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  160. The LIM Domain Homeobox Gene isl-1 is a positive regulator of Thyrostimulin subunit, GPA2 gene Transcription. International conference

    Chizuko Suzuki, Hiroshi Nagasaki, Yoshiki Okajima, Hidetaka Suga, Yasumasa Iwasaki, Yutaka Oiso.

    The 87th annual meeting, The Endocrine Society 2006. 

     More details

    Event date: 2006.6

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  161. The role of the Oligosaccharide Chains of Thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits, GPA2 and GPB5. International conference

    Yoshiki Okajima, Hiroshi Nagasaki, Chizuko Suzuki, Hidetaka Suga, Yutaka Oiso.

    The Endocrine Society 2006. 

     More details

    Event date: 2006.6

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  162. サイロスティムリンにおける糖鎖の生化学的役割についての検討.

    岡島由樹, 鈴木千津子, 須賀英隆, 長崎弘, 大磯ユタカ

    第79回日本内分泌学会学術総会 

     More details

    Event date: 2006.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  163. LIM Domain Homeobox gene,isl-1によるサイロスティムリン サブユニット,GPA2の転写調節.

    鈴木千津子, 岡島由樹, 須賀英隆, 長崎弘, 大磯ユタカ

    第79回日本内分泌学会学術総会 

     More details

    Event date: 2006.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  164. 重症薬疹後に非自己免疫性1型糖尿病とGraves病を発症した1例.

    遠藤茂樹, 須賀英隆, 松田淳一

    第14回臨床内分泌代謝Update. 

     More details

    Event date: 2004.3

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  165. 化学療法が無効で,内照射治療により腫瘍抑制が得られた悪性褐色細胞腫の1例.

    田口晴子, 稲垣朱実, 岡島由樹, 深見亜也子, 太田貴美子, 須賀英隆, 加藤朋子, 垣屋聡, 板津武晴, 佐藤公治, 氏平伸子, 横山邦彦

    第76回日本内分泌学会学術総会 

     More details

    Event date: 2003.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  166. Paclitaxelによる化学療法が有効であった甲状腺未分化癌の一例.

    須賀英隆, 稲垣朱実, 太田貴美子, 深見亜也子, 岡島由樹, 加藤朋子, 垣屋聡, 板津武晴, 氏平伸子.

    第76回日本内分泌学会学術総会 

     More details

    Event date: 2003.5

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  167. 著明な高Ca血症を呈したPTH-rP産生膵腫瘍の一例.

    岡島由樹, 稲垣朱実, 深見亜也子, 須賀英隆, 垣屋聡, 板津武晴, 水野隆史, 長谷川洋, 氏平伸子

    第13回臨床内分泌代謝Update 

     More details

    Event date: 2003.3

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  168. 劇症1型糖尿病の2例.

    垣屋聡, 稲垣朱実, 岡島由樹, 深見亜也子, 須賀英隆, 板津武晴

    第67回日本糖尿病学会中部地方会 

     More details

    Event date: 2003.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  169. 副腎静脈血カテコラミン異常高値を認めた副腎pseudocystの一例.

    須賀英隆, 稲垣朱実, 太田貴美子, 田口晴子, 板津武晴, 横井圭介, 小林弘明, 都築豊徳

    第12回臨床内分泌代謝Update 

     More details

    Event date: 2002.3

    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  170. 疾患特異的iPS細胞を用いた先天性下垂体機能低下症の病態解明

    松本 隆作, 須賀 英隆, 青井 貴之, 坂東 弘教, 福岡 秀規, 井口 元三, 鳴海 覚志, 高木 優樹, 石井 智弘, 長谷川 奉延, 六車 恵子, 小川 渉, 高橋 裕

    第90回日本内分泌学会総会  2017.4.20 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  171. 家族性中枢性尿崩症疾患特異的iPS細胞を用いた4-PBAによる治療の可能性

    光本一樹, 須賀英隆, 有馬寛

    第92回日本内分泌学会学術総会  2019.5.9 

     More details

    Language:Japanese   Presentation type:Poster presentation  

  172. 下垂体発生における視床下部-口腔外胚葉間FGFの役割

    松本 隆作, 青井 貴之, 小柳 三千代, 須賀 英隆, 福岡 秀規, 井口 元三, 小川 渉, 高橋 裕

    第92回日本内分泌学会学術総会  2019.5.9 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  173. 下垂体分化における視床下部隣接の意義

    須賀 英隆, 笠井 貴敏, 有馬 寛

    第32回日本下垂体研究会学術集会  2017.8.2 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  174. 下垂体再生医療の現状と将来像 Invited

    須賀 英隆

    第16回日本再生医療学会総会  2017.3.7 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  175. 下垂体の再生医療 Invited

    須賀 英隆

    厚生労働科学研究費補助金難治性疾患等政策研究事業 (難治性疾患政策研究事業)間脳下垂体機能障害に関する調査研究班 市民公開講座  2019.1.27 

     More details

    Language:English  

  176. マウス胚性幹細胞由来AVP神経の電気生理学的特性

    金子 葉子, 大熊 真人, 小谷 侑, 須賀 英隆, 中島 昭, 宮地 栄一, 長崎 弘

    第44回日本神経内分泌学会学術集会  2017.10.21 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  177. マウスES細胞から分化誘導した視床下部神経幹細胞

    須賀英隆, 加納麻弓子, 有馬寛

    第34回下垂体研究会学術集会  2019.8.7 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  178. ヒト多能性幹細胞由来3次元培養視床下部/下垂体組織の形態学的検討 第1報

    井下尚子, 須賀英隆

    第34回下垂体研究会学術集会  2019.8.7 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  179. ヒト多能性幹細胞を用いた視床下部・下垂体研究 Invited

    須賀 英隆

    第4回NLS(ナノライフシステム)セミナー  2019.11.12 

     More details

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  180. ヒトiPS細胞を用いたin vitro ACTH産生細胞成熟機構の解明と腫瘍モデル作成の試み

    松本 隆作, 須賀 英隆, 青井 貴之, 福岡 秀規, 井口 元三, 小武 由紀子, 吉田 健一, 坂東 弘教, 隅田 健太郎, 西沢 衡, 小川 渉, 高橋 裕

    第27回日本間脳下垂体腫瘍学会  2017.2.24 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  181. ヒトiPS細胞から下垂体PRL産生細胞への分化誘導

    永井孝, 須賀英隆, 大須賀智子, 有馬寛

    第92回日本内分泌学会学術総会  2019.5.11 

     More details

    Language:Japanese   Presentation type:Poster presentation  

  182. ヒトES/iPS細胞から機能的な下垂体前葉の試験管内誘導

    大曽根 親文, 須賀 英隆, 辻 孝, 笹井 芳樹, 有馬 寛

    第90回日本内分泌学会総会  2017.4.20 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  183. iPS細胞を利用した視床下部‐下垂体の医療 Invited

    須賀 英隆

    あいちサイエンスフェスティバルサイエンストーク  2019.10.29 

     More details

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  184. in vitro下垂体分化法を生体により近づける試み Invited

    須賀 英隆

    第44回日本神経内分泌学会学術集会  2017.10.21 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  185. In vitroで挑戦する視床下部・下垂体の発生と分化再現 Invited

    須賀 英隆, 大曽根 親文, 小川 晃一郎, 笠井 貴敏, 有馬 寛

    第35回内分泌代謝学サマーセミナー  2017.7.13 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  186. ES/iPS細胞を用いた視床下部・下垂体再生医療と病理への展開 Invited

    須賀英隆, 松本隆作, 有馬寛

    第23回日本臨床内分泌病理学会学術総会  2019.10.5 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  187. 疾患特異的iPS細胞を用いた家族性中枢性尿崩症の病態解明

    光本一樹, 須賀 英隆, 山田登美子, 加納麻弓子, 橡谷昌佳, 大曽根親文, 笠井貴敏, 萩原大輔, 有馬寛

    第二回医薬系3部局交流シンポジウム  2017.6.16 

     More details

    Language:Japanese   Presentation type:Poster presentation  

  188. 間脳下垂体における再生医療 Invited

    須賀 英隆

    第29回日本間脳下垂体腫瘍学会  2019.2.22 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  189. 試験管で作る下垂体 Invited

    須賀英隆, 有馬寛

    第3回Young Rising Seminar  2017.5.12 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  190. 視床下部・下垂体疾患に対する再生医療 Invited

    須賀 英隆, 有馬 寛

    第18回日本再生医療学会総会  2019.3.21 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  191. 視床下部・下垂体の再生医療に向けて Invited

    須賀 英隆

    静岡内分泌研究会  2017.3.16 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  192. 視床下部・下垂体の再生医療および病態研究

    須賀 英隆

    第2回内分泌アゴラ  2017.1.30 

     More details

    Language:English   Presentation type:Oral presentation (general)  

  193. 視床下部・下垂体の再生医療および病態研究 Invited

    須賀 英隆

    京都大学ウイルス・再生医科学研究所セミナー  2017.7.21 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  194. 立体培養による視床下部・下垂体の誘導と成熟 Invited

    須賀 英隆

    第27回日本間脳下垂体腫瘍学会  2017.2.24 

     More details

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  195. 立体培養による視床下部・下垂体の誘導 Invited

    須賀英隆, 有馬寛

    第90回日本内分泌学会総会  2017.4.20 

     More details

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  196. 疾患特異的iPS細胞を用いた家族性中枢性尿崩症の病態解明

    光本 一樹, 須賀 英隆, 山田 登美子, 加納 麻弓子, 橡谷 昌佳, 大曽根 親文, 笠井 貴敏, 萩原 大輔, 有馬 寛

    第90回日本内分泌学会総会  2017.4.20 

     More details

    Language:Japanese   Presentation type:Poster presentation  

  197. ES/iPS細胞から視床下部‐下垂体組織の作製 Invited

    須賀英隆

    第126回日本解剖学会総会・全国学術集会/第98回日本生理学会大会合同大会  2021.3.28 

     More details

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  198. ラトケ嚢胞に中枢性尿崩症を合併した1例

    尾崎創, 山田沙矢加, 宮田崇, 髙木博史, 須賀英隆, 有馬寛

    日本内科学会第244回東海地方会  2021.6.27 

     More details

    Language:Japanese   Presentation type:Oral presentation (general)  

  199. シャーレの上の視床下部-下垂体 Invited

    須賀英隆, 有馬寛

    第3回最先端循環代謝学の若手研究会  2021.12.8 

     More details

    Language:English   Presentation type:Oral presentation (general)  

  200. 視床下部・下垂体の再生医療研究 Invited

    須賀英隆, 有馬寛

    Kidney & Endocrine Researchers Web Seminar  2021.11.16 

     More details

    Language:English   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

▼display all

Research Project for Joint Research, Competitive Funding, etc. 7

  1. 臨床用ヒトiPS細胞から誘導した精製下垂体による再生医療開発

    2024.4 - 2027.3

    難治性疾患実用化研究事業 

      More details

    Authorship:Principal investigator 

  2. ヒト多能性幹細胞を用いた下垂体前葉機能低下症への再生医療技術開発

    2021.4 - 2024.3

    難治性疾患事業実用化研究事業 

      More details

    Authorship:Principal investigator  Grant type:Competitive

  3. ヒト脳神経発生を正確に再現し、測れなかったものを測る

    2021.1 - 2028.3

    創発的研究支援事業 

      More details

    Authorship:Principal investigator 

  4. ヒト多能性幹細胞を用いた下垂体機能低下症に対する再生医療の技術開発

    2018.10 - 2021.3

    再生医療実現拠点ネットワークプログラム 

    須賀英隆

      More details

    Grant type:Competitive

  5. 疾患モデル高度化による視床下部・下垂体難病研究

    2017.8 - 2020.3

    再生医療実現拠点ネットワークプログラム 

    須賀英隆

      More details

    Grant type:Competitive

  6. ヒトiPS 細胞を用いた視床下部-下垂体ホルモン産生細胞の分化誘導法と移植方法の開発

    2015.4 - 2018.3

    再生医療実現拠点ネットワークプログラム 

    須賀英隆

      More details

    Grant type:Competitive

  7. ヒトiPS 細胞を用いた視床下部-下垂体ホルモン産生細胞の分化誘導法と移植方法の開発

    2013.4 - 2015.3

    再生医療実現拠点ネットワークプログラム 

      More details

    Grant type:Competitive

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 15

  1. 微小血管を配備した視床下部ー下垂体系オルガノイドの灌流培養システムの構築

    Grant number:23H03777  2023.4 - 2028.3

    科学研究費助成事業  基盤研究(B)

    杉浦 慎治, 須賀 英隆

      More details

    Authorship:Coinvestigator(s) 

    近年、幹細胞より誘導された様々な臓器のオルガノイドが開発され、再生医療や創薬開発
    への応用が期待されている。一方、内分泌器官などのように組織内に血管網を有する臓器のオルガノイドを構築するためにはオルガノイドへ血管網を配備し、そこに培養液を灌流することが理想的と考えられるが、現時点でこれを実現する手法は確立されていない。本研究では、研究代表者の杉浦が独自に開発してきた微小血管の灌流培養システムを活用し、研究分担者の須賀が構築する視床下部-下垂体原基へ血管を配備して培養液を灌流することで、高次機能を発現する"真の視床下部-下垂体系オルガノイド"を構築する。

  2. ヒト多能性幹細胞から下垂体前葉の幹細胞作出とその性質検討

    Grant number:23K080005  2023.4 - 2026.3

    日本学術振興会  科学研究費補助金  基盤研究(C)

      More details

    Authorship:Principal investigator 

  3. Generation and characterization of anterior pituitary stem cells from human pluripotent stem cells

    Grant number:23K08005  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

      More details

    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

  4. Generation of novel human ACTH cells and their application to the treatment of pituitary intractable diseases

    Grant number:22K08657  2022.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

      More details

    Authorship:Coinvestigator(s) 

  5. Development of band-edge-defective near-infrared fluorescent quantum dots for deep biological temperature imaging measurement

    Grant number:22H03938  2022.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

      More details

    Authorship:Coinvestigator(s) 

  6. 下垂体後葉機能に対する病理学的アプローチ

    Grant number:22K06993  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    井下 尚子, 須賀 英隆, 須賀 英隆

      More details

    Authorship:Coinvestigator(s) 

    後葉ホルモンは、抗利尿ホルモンであるバソプレシンと、子宮収縮/陣痛誘発を行うオキシトシンであるが、いずれも視床下部で産生され、後葉に運ばれ貯蔵、分泌される。病理解剖症例の経験では、後葉ホルモン貯蔵量を反映すると考えられる後葉内の視床下部神経末端の大きさは、超高齢者、長期臥床例でほぼ枯渇する。
    病理解剖検体に組織学的検討、バソプレシン、オキシトシン、浸透圧センサー等の免疫染色を加え形態学的に、後葉機能が関わる死因や疾患を考える。さらに培養系ではiPS細胞由来視床下部/下垂体組織において、浸透圧負荷等による変化を、電顕レベルの超微構造、免疫電顕を用いたタンパク発現解析を用いて検討する。
    下垂体後葉機能に対する病理学的アプローチを行うために、本年度は、解剖例における症例収集、既存の、病理診断業務の範囲で作成された標本の収集、検討を行った。
    下垂体そのものは、病理解剖時に脳をとることの許可をいただければ、ルーチンで標本を作製するので、今までに遡って30例以上の標本をHE染色にて検討している。後葉に線維を送るバソプレシン、オキシトシンニューロンは、視床下部室傍核や視索上核に存在し、今回ターゲットとする一つであるASK3は動物では同部位に存在することが知られているため、第3脳室周囲の追加切り出しを行い標本作成した。また前向きに2022年からは下垂体茎を座切りにするなど、視床下部から下垂体へのシグナル、線維の走行、その線維が陽性となるホルモン等が同定できるように配慮した切り出しを行うように心がけて標本作成を行った。
    結果、室傍核や視索上核に加え、下垂体門脈へのホルモンが集まる正中隆起なども同定することができた。下垂体茎部では、視床下部から後葉に繋がる線維の横断面を確認し、また前葉と同じホルモン産生細胞からなるPars tubularisを確認するとともに、多数の血管、血管網を認めた。これらが下垂体門脈に相当すると考えられた。
    また、後葉ではへリング体と呼ばれる神経末端があるが、症例によりこの面積に差があること、また、Basophil invasionという老化やアルツハイマー病で顕著となる細胞増殖を認める症例も集めることができた。
    現在までの標本作成、検討で、目的とする神経核の同定、組織所見の収集ができている。また、この部位は、あまり検討がなされていない領域であるため、想定以上に新たな所見が集められている。
    収集した標本に対して、免疫染色を追加し、各ホルモン産生あるいはタンパク陽性細胞の視床下部での分布、あるいは、後葉への線維の走行パターンなどを詳細に検討する。

  7. Establishment of the system for predicting pituitary dysfunction induced by immune checkpoint inhibitors

    Grant number:22H03127  2022.4 - 2025.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

      More details

    Authorship:Coinvestigator(s) 

  8. ヒト脳神経発生を正確に再現し、測れなかったものを測る

    2021.1 - 2028.3

    科学技術振興機構(JST)  創発的研究支援事業  2020創発的研究支援事業

      More details

    Authorship:Principal investigator 

  9. Generation of hypothalamic neural stem cells in vitro from human pluripotent stem cells

    Grant number:20K08859  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Suga Hidetaka

      More details

    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    In this study, we induced human hypothalamic neural tissue organoids using human ESCs (hESCs), attempted to fractionate hypothalamic neural stem cell-like cells from the organoids, and examined whether these fractionated cells have tissue stem cell properties.
    We focused on RAX and differentiated RAX::VENUS knock-in hESCs into hypothalamic organoids and sorted RAX-positive cells from mature organoids. The isolated RAX-positive cells formed neurospheres and exhibited self-renewal and multipotency. Neurogenesis was observed when neurospheres were transplanted into the mouse hypothalamus. We isolated RAX-positive hypothalamic neural stem cell-like cells from wild-type human ES organoids. This is the first study to differentiate human hypothalamic neural stem cell-like cells from pluripotent stem cells.

  10. Ultrastructural studies on differentiation of pluripotent stem cells to pituitary cells

    Grant number:19K07427  2019.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

      More details

    Authorship:Coinvestigator(s) 

    Grant amount:\120000

  11. ヒト多能性幹細胞を用いた下垂体機能低下症に対する再生医療の技術開発

    2018.10 - 2021.3

    日本医療研究開発機構  再生医療実現拠点ネットワークプログラム(技術開発個別課題) 

    須賀 英隆

      More details

    Authorship:Principal investigator  Grant type:Competitive

  12. 疾患モデル高度化による視床下部・下垂体難病研究

    2017.8 - 2020.3

    日本医療研究開発機構  再生医療実現拠点ネットワークプログラム(疾患特異的iPS細胞の利活用促進・難病研究加速プログラム) 

    須賀 英隆

      More details

    Authorship:Principal investigator  Grant type:Competitive

  13. 多能性幹細胞から視床下部と下垂体の機能的ユニットを作る

    Grant number:17K09878  2017.4 - 2020.3

    日本学術振興会  科学研究費補助金(基盤研究C) 

    須賀 英隆

      More details

    Authorship:Principal investigator  Grant type:Competitive

  14. マウス疾患特異的iPS細胞を用いた遺伝性中枢性尿崩症in vitro実験系の確立

    Grant number:26461379  2014.4 - 2017.3

    日本学術振興会  科学研究費補助金(基盤研究C) 

    須賀 英隆

      More details

    Authorship:Principal investigator  Grant type:Competitive

  15. ヒトiPS細胞を用いた視床下部-下垂体ホルモン産生細胞の分化誘導法と移植方法の開発

    2013.4 - 2018.3

    日本医療研究開発機構  再生医療実現拠点ネットワークプログラム(技術開発個別課題) 

    須賀 英隆

      More details

    Authorship:Principal investigator  Grant type:Competitive

▼display all

Industrial property rights 14

  1. 下垂体ホルモン産生細胞の移植

    須賀英隆, 佐々木博勇, 桑原篤, 多賀詩織, 中野徳重

     More details

    Applicant:国立大学法人東海国立大学機構、住友ファーマ株式会社、住友化学株式会社

    Application no:特願2023-021207  Date applied:2023.2

  2. 下垂体ホルモン産生細胞を含む細胞凝集体及びその製造方法

    多賀詩織, 桑原篤, 須賀英隆, 中野徳重

     More details

    Application no:特願2021-162253  Date applied:2021.9

  3. 下垂体組織を含む細胞集団の製造方法及びその細胞集団

    中野徳重, 多賀詩織, 桑原篤, 須賀英隆

     More details

    Application no:特願2021-162255  Date applied:2021.9

  4. 表面細胞マーカーを用いた下垂体細胞および視床下部細胞の分離法

    小谷侑, 河田美穂, 長崎弘, 須賀英隆

     More details

    Applicant:学校法人藤田学園、国立大学法人東海国立大学機構

    Application no:特願2021-158406  Date applied:2021.9

  5. 下垂体ホルモン産生細胞及びその前駆細胞の分離法

    小谷侑, 長崎弘, 須賀英隆

     More details

    Applicant:学校法人藤田学園、国立大学法人東海国立大学機構

    Application no:特願2020-065346  Date applied:2020.3

    Publication no:WO2021/201175 A1  Date published:2021.10

  6. 細胞培養容器および細胞培養方法

    須賀英隆, 有馬寛, 榊原真弓, 杉浦慎治, 田村 磨聖, 佐藤 琢, 長崎 玲子, 長崎 晃, 金森 敏幸

     More details

    Application no:特願2018-006810  Date applied:2018.1

  7. ヒト多能性幹細胞から視床下部ニューロンへの分化誘導法

    須賀英隆, 小川晃一郎, 笠井貴敏, 有馬寛

     More details

    Application no:特願2016-010940  Date applied:2016.1

    Announcement no:特開WO2017126551  Date announced:2017.2

    Patent/Registration no:特許7023496  Date issued:2022.2

  8. ヒト多能性幹細胞から視床下部ニューロンへの分化誘導法

    須賀英隆,小川晃一郎,笠井貴敏,有馬寛

     More details

    Applicant:須賀英隆, 小川晃一郎, 笠井貴敏, 有馬寛

    Application no:特願2016-010940  Date applied:2016.1

    Country of applicant:Domestic  

  9. 腺性下垂体又はその前駆組織の製造方法

    笹井芳樹, 大曽根親文, 須賀英隆

     More details

    Applicant:笹井芳樹, 大曽根親文, 須賀英隆

    Application no:特願2014-152384  Date applied:2014.7

    Country of applicant:Domestic  

  10. 腺性下垂体又はその前駆組織の製造方法

    笹井芳樹, 大曽根親文, 須賀英隆

     More details

    Application no:特願2014-152384  Date applied:2014.7

    Patent/Registration no:特許6789814  Date registered:2022.2  Date issued:2022.3

  11. 幹細胞の培養方法

    笹井芳樹, 須賀英隆

     More details

    Application no:特願2011-239803  Date applied:2011.10

    Patent/Registration no:特許6516810  Date registered:2019.4 

  12. 幹細胞の培養方法.

    笹井芳樹, 須賀英隆.

     More details

    Application no:2011-239803.  Date applied:2011

    Country of applicant:Domestic  

  13. 腎性尿崩症治療用組換えベクター及びその用途.

    長崎弘, 須賀英隆, 大磯ユタカ, 井上誠, 長谷川護.

     More details

    Application no:2007-232310  Date applied:2007

    Country of applicant:Domestic  

  14. 下垂体ホルモン産生細胞の移植

    須賀英隆、佐々木博勇、桑原篤、多賀詩織、中野徳重

     More details

    Applicant:東海国立大学機構,住友ファーマ株式会社、住友化学株式会社

    Application no:特願2023-021207 

    Date announced:2023.2

▼display all