記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

OBJECTIVE: To establish and characterize cell lines derived from human endometrial epithelial cells (ECs) and mesenchymal cells (MCs) from patients with and without endometriosis. DESIGN: In vitro experimental study. SETTING: University and national cancer center research institute. PATIENT(S): Two women with endometriosis and two women without endometriosis. INTERVENTION(S): Sampling of endometrial ECs and MCs. MAIN OUTCOME MEASURE(S): Establishing immortalized endometrial ECs and MCs with quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunocytochemical analysis, and RNA sequence profiling performed to characterize the immortalized cells and a cell proliferation assay, three-dimensional culture, and assays for hormone responses performed to characterize the features of ECs. RESULT(S): The qRT-PCR, immunocytochemical analysis, and Western blot analysis revealed that the ECs and MCs maintained their original features. Moreover, the immortalized cells were found to retain responsiveness to sex steroid hormones. The ECs formed a gland-like structure in three-dimensional culture, indicating the maintenance of normal EC phenotypes. The RNA sequence profiling, principal component analysis, and clustering analysis showed that the gene expression patterns of the immortalized cells were different from those of cancer cells. Several signaling pathways that were statistically significantly enriched in ECs and MCs with endometriosis were revealed. CONCLUSION(S): We successfully obtained four paired immortalized endometrial ECs and MCs from patients with and without endometriosis. Using these cells could help identify diagnostic and therapeutic targets for endometriosis. The cell lines established in this study will thus serve as powerful experimental tools in the study of endometriosis.

DOI： 10.1016/j.xfss.2020.09.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41388-020-01393-x

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その他リンク： https://www.nature.com/articles/s41388-020-01393-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0233782

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase (IDH) status. Although IDH-wild-type diffuse astrocytic glioma (DAG) shows a more aggressive phenotype than IDH-mutant type, lack of knowledge regarding relevant molecular drivers for this type of tumor has hindered the development of therapeutic agents. Here, we examined human IDH-wild-type DAGs and a glioma mouse model with a mosaic analysis with double markers (MADM) system, which concurrently lacks p53 and NF1 and spontaneously develops tumors highly comparable with human IDH-wild-type DAG without characteristic molecular features of glioblastoma (DAG-nonMF). During tumor formation, enhancer of zeste homolog (EZH2) and the other polycomb repressive complex 2 (PRC2) components were upregulated even at an early stage of tumorigenesis, together with an increased number of genes with H3K27me3 or H3K27me3 and H3K4me3 bivalent modifications. Among the epigenetically dysregulated genes, frizzled-8 (Fzd8), which is known to be a cancer- and stem cell reprogramming-related gene, was gradually silenced during tumorigenesis. Genetic and pharmacologic inhibition of EZH2 in MADM mice showed reactivation of aberrant H3K27me3 target genes, including Fzd8, together with significant reduction of tumor size. Our study clarifies a pathogenic molecular pathway of IDH-wild-type DAG-nonMF that depends on EZH2 activity and provides a strong rationale for targeting EZH2 as a promising therapeutic approach for this type of glioma. SIGNIFICANCE: EZH2 is involved in the generation of IDH-wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4814/F1.large.jpg.

DOI： 10.1158/0008-5472.CAN-19-1272

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The initiation of embryonic gene expression in ascidian embryos appears to be tightly regulated by the number of DNA replication cycles. DNA methylation is thought to contribute to the clock mechanism that counts the rounds of DNA replication. We used mass spectrometry and whole genome bisulfite sequencing to characterize DNA methylation changes that occur in early developmental stages of the ascidian, Ciona intestinalis. We found that global DNA methylation in early Ciona development was static, and a base-wise comparison between the genomes of consecutive developmental stages found no DNA demethylation that was related to zygotic gene activation. Additionally, 5hmC was hardly detected by mass spectrometry in the developmental samples, suggesting a lack of demethylation mediated by ten eleven translocation (TET) methylcytosine dioxygenase in C. intestinalis. We conclude that DNA methylation is not involved in regulating DNA replication-dependent transcriptional activation. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygeno.2016.10.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1756-8935-6-38

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00438-009-0500-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

The genomes of many animals, plants and fungi are tagged by methylation of DNA cytosine. To understand the biological significance of this epigenetic mark it is essential to know where in the genome it is located. New techniques are making it easier to map DNA methylation patterns on a large scale and the results have already provided surprises. In particular, the conventional view that DNA methylation functions predominantly to irreversibly silence transcription is being challenged. Not only is promoter methylation often highly dynamic during development, but many organisms also seem to target DNA methylation specifically to the bodies of active genes.

DOI： 10.1038/nrg2341

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1101/gr.6163007

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Web of Science

開催年月日： 2023年6月

会議種別：ポスター発表  

開催年月日： 2022年10月 - 2022年11月

会議種別：口頭発表（招待・特別）  

開催年月日： 2022年6月

会議種別：ポスター発表  

開催年月日： 2022年2月

会議種別：口頭発表（招待・特別）  

開催年月日： 2021年3月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：オンライン  

開催年月日： 2021年3月

会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2020年12月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催年月日： 2020年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（指名）  

開催地：沼津  

記述言語：英語   会議種別：ポスター発表  

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会議種別：シンポジウム・ワークショップ パネル（指名）  

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記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（指名）  

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会議種別：ポスター発表  

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会議種別：口頭発表（一般）  

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会議種別：シンポジウム・ワークショップ パネル（指名）  

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