2024/10/10 更新

写真a

コンドウ ヨウヘイ
近藤 洋平
KONDO Yohei
所属
One Medicine 生命-創薬共創プラットフォーム データサイエンス部門 特任講師
職名
特任講師

学位 2

  1. 博士(学術) ( 2013年5月   東京大学 ) 

  2. 修士(学術) ( 2010年3月   東京大学 ) 

経歴 5

  1. One Medicine 生命-創薬共創プラットフォーム   特任講師

    2024年10月 - 現在

  2. 京都大学大学院 生命科学研究科 細胞周期学分野   特定准教授

    2024年4月 - 2024年10月

  3. 自然科学研究機構 生命創成探求センター   定量生物学研究グループ   助教

    2024年3月 - 現在

  4. 自然科学研究機構   基礎生物学研究所   助教

    2017年 - 2018年

  5. 京都大学大学院   情報学研究科   特任助教

    2013年 - 2018年

所属学協会 2

  1. 日本生物物理学会

  2. 日本分子生物学会

 

論文 30

  1. Revisiting the evolution of bow-tie architecture in signaling networks. 国際誌

    Thoma Itoh, Yohei Kondo, Kazuhiro Aoki, Nen Saito

    NPJ systems biology and applications   10 巻 ( 1 ) 頁: 70 - 70   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Bow-tie architecture is a layered network structure that has a narrow middle layer with multiple inputs and outputs. Such structures are widely seen in the molecular networks in cells, suggesting that a universal evolutionary mechanism underlies the emergence of bow-tie architecture. The previous theoretical studies have implemented evolutionary simulations of the feedforward network to satisfy a given input-output goal and proposed that the bow-tie architecture emerges when the ideal input-output relation is given as a rank-deficient matrix with mutations in network link intensities in a multiplicative manner. Here, we report that the bow-tie network inevitably appears when the link intensities representing molecular interactions are small at the initial condition of the evolutionary simulation, regardless of the rank of the goal matrix. Our dynamical system analysis clarifies the mechanisms underlying the emergence of the bow-tie structure. Further, we demonstrate that the increase in the input-output matrix reduces the width of the middle layer, resulting in the emergence of bow-tie architecture, even when evolution starts from large link intensities. Our data suggest that bow-tie architecture emerges as a side effect of evolution rather than as a result of evolutionary adaptation.

    DOI: 10.1038/s41540-024-00396-8

    PubMed

  2. Microtubule-associated phase separation of MIDD1 tunes cell wall spacing in xylem vessels in <i>Arabidopsis thaliana</i>

    Higa, T; Kijima, ST; Sasaki, T; Takatani, S; Asano, R; Kondo, Y; Wakazaki, M; Sato, M; Toyooka, K; Demura, T; Fukuda, H; Oda, Y

    NATURE PLANTS   10 巻 ( 1 ) 頁: 100 - +   2024年1月

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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 Plants  

    Properly patterned cell walls specify cellular functions in plants. Differentiating protoxylem and metaxylem vessel cells exhibit thick secondary cell walls in striped and pitted patterns, respectively. Cortical microtubules are arranged in distinct patterns to direct cell wall deposition. The scaffold protein MIDD1 promotes microtubule depletion by interacting with ROP GTPases and KINESIN-13A in metaxylem vessels. Here we show that the phase separation of MIDD1 fine-tunes cell wall spacing in protoxylem vessels in Arabidopsis thaliana. Compared with wild-type, midd1 mutants exhibited narrower gaps and smaller pits in the secondary cell walls of protoxylem and metaxylem vessel cells, respectively. Live imaging of ectopically induced protoxylem vessels revealed that MIDD1 forms condensations along the depolymerizing microtubules, which in turn caused massive catastrophe of microtubules. The MIDD1 condensates exhibited rapid turnover and were susceptible to 1,6-hexanediol. Loss of ROP abolished the condensation of MIDD1 and resulted in narrow cell wall gaps in protoxylem vessels. These results suggest that the microtubule-associated phase separation of MIDD1 facilitates microtubule arrangement to regulate the size of gaps in secondary cell walls. This study reveals a new biological role of phase separation in the fine-tuning of cell wall patterning.

    DOI: 10.1038/s41477-023-01593-9

    Web of Science

    Scopus

    PubMed

    その他リンク: https://www.nature.com/articles/s41477-023-01593-9

  3. Live-cell imaging defines a threshold in CDK activity at the G2/M transition

    Hironori Sugiyama, Yuhei Goto, Yohei Kondo, Damien Coudreuse, Kazuhiro Aoki

    Developmental Cell     2024年1月

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

    DOI: 10.1016/j.devcel.2023.12.014

  4. A transcriptional program underlying the circannual rhythms of gonadal development in medaka

    Tomoya Nakayama, Miki Tanikawa, Yuki Okushi, Thoma Itoh, Tsuyoshi Shimmura, Michiyo Maruyama, Taiki Yamaguchi, Akiko Matsumiya, Ai Shinomiya, Ying-Jey Guh, Junfeng Chen, Kiyoshi Naruse, Hiroshi Kudoh, Yohei Kondo, Honda Naoki, Kazuhiro Aoki, Atsushi J. Nagano, Takashi Yoshimura

    Proceedings of the National Academy of Sciences   120 巻 ( 52 )   2023年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Proceedings of the National Academy of Sciences  

    To cope with seasonal environmental changes, organisms have evolved approximately 1-y endogenous circannual clocks. These circannual clocks regulate various physiological properties and behaviors such as reproduction, hibernation, migration, and molting, thus providing organisms with adaptive advantages. Although several hypotheses have been proposed, the genes that regulate circannual rhythms and the underlying mechanisms controlling long-term circannual clocks remain unknown in any organism. Here, we show a transcriptional program underlying the circannual clock in medaka fish ( Oryzias latipes ). We monitored the seasonal reproductive rhythms of medaka kept under natural outdoor conditions for 2 y. Linear regression analysis suggested that seasonal changes in reproductive activity were predominantly determined by an endogenous program. Medaka hypothalamic and pituitary transcriptomes were obtained monthly over 2 y and daily on all equinoxes and solstices. Analysis identified 3,341 seasonally oscillating genes and 1,381 daily oscillating genes. We then examined the existence of circannual rhythms in medaka via maintaining them under constant photoperiodic conditions. Medaka exhibited approximately 6-mo free-running circannual rhythms under constant conditions, and monthly transcriptomes under constant conditions identified 518 circannual genes. Gene ontology analysis of circannual genes highlighted the enrichment of genes related to cell proliferation and differentiation. Altogether, our findings support the “histogenesis hypothesis” that postulates the involvement of tissue remodeling in circannual time-keeping.

    DOI: 10.1073/pnas.2313514120

  5. In-Depth Quantification of Cell Division and Elongation Dynamics at the Tip of Growing Arabidopsis Roots Using 4D Microscopy, AI-Assisted Image Processing and Data Sonification

    Tatsuaki Goh, Yu Song, Takaaki Yonekura, Noriyasu Obushi, Zeping Den, Katsutoshi Imizu, Yoko Tomizawa, Yohei Kondo, Shunsuke Miyashima, Yutaro Iwamoto, Masahiko Inami, Yen-Wei Chen, Keiji Nakajima

    Plant And Cell Physiology   64 巻 ( 11 ) 頁: 1262 - 1278   2023年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    One of the fundamental questions in plant developmental biology is how cell proliferation and cell expansion coordinately determine organ growth and morphology. An amenable system to address this question is the Arabidopsis root tip, where cell proliferation and elongation occur in spatially separated domains, and cell morphologies can easily be observed using a confocal microscope. While past studies revealed numerous elements of root growth regulation including gene regulatory networks, hormone transport and signaling, cell mechanics and environmental perception, how cells divide and elongate under possible constraints from cell lineages and neighboring cell files has not been analyzed quantitatively. This is mainly due to the technical difficulties in capturing cell division and elongation dynamics at the tip of growing roots, as well as an extremely labor-intensive task of tracing the lineages of frequently dividing cells. Here, we developed a motion-tracking confocal microscope and an Artificial Intelligence (AI)-assisted image-processing pipeline that enables semi-automated quantification of cell division and elongation dynamics at the tip of vertically growing Arabidopsis roots. We also implemented a data sonification tool that facilitates human recognition of cell division synchrony. Using these tools, we revealed previously unnoted lineage-constrained dynamics of cell division and elongation, and their contribution to the root zonation boundaries.

    DOI: 10.1093/pcp/pcad105

    その他リンク: https://academic.oup.com/pcp/article-pdf/64/11/1262/54040944/pcad105.pdf

  6. Harnessing Deep Learning to Analyze Cryptic Morphological Variability of <i>Marchantia polymorpha</i>.

    Yoko Tomizawa, Naoki Minamino, Eita Shimokawa, Shogo Kawamura, Aino Komatsu, Takuma Hiwatashi, Ryuichi Nishihama, Takashi Ueda, Takayuki Kohchi, Yohei Kondo

    Plant And Cell Physiology     2023年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Oxford University Press (OUP)  

    Abstract

    Characterizing phenotypes is a fundamental aspect of biological sciences, although it can be challenging due to various factors. For instance, the liverwort (Marchantia polymorpha), a model system for plant biology, exhibits morphological variability, making it difficult to identify and quantify distinct phenotypic features using objective measures. To address this issue, we utilized a deep learning-based image classifier that can handle plant images directly without manual extraction of phenotypic features, and analyzed pictures of M. polymorpha. This dioicous plant species exhibits morphological differences between male and female wild accessions at an early stage of gemmaling growth, although it remains elusive whether the differences are attributable to sex chromosomes. To isolate the effects of sex chromosomes from autosomal polymorphisms, we established a male and female set of recombinant inbred lines (RILs) from a set of male and female wild accessions. We then trained deep-learning models to classify the sexes of the RILs and the wild accessions. Our results showed that the trained classifiers accurately classified male and female gemmalings of wild accessions in the first week of growth, confirming the intuition of researchers in a reproducible and objective manner. In contrast, the RILs were less distinguishable, indicating that the differences between the parental wild accessions arose from autosomal variations. Furthermore, we validated our trained models by an “explainable AI” technique that highlights image regions relevant to the classification. Our findings demonstrate that the classifier-based approach provides a powerful tool for analyzing plant species that lack standardized phenotyping metrics.

    DOI: 10.1093/pcp/pcad117

  7. Cytoplasmic fluidization triggers breaking spore dormancy in fission yeast.

    Keiichiro Sakai, Yohei Kondo, Yuhei Goto, Kazuhiro Aoki

        2023年9月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    The cytoplasm is a complex, crowded environment that influences myriad cellular processes including protein folding and metabolic reactions. Recent studies have suggested that changes in the biophysical properties of the cytoplasm play a key role in cellular homeostasis and adaptation. However, it still remains unclear how cells control their cytoplasmic properties in response to environmental cues. Here, we used fission yeast spores as a model system of dormant cells to elucidate the mechanisms underlying regulation of the cytoplasmic properties. By tracking fluorescent tracer particles, we found that particle mobility decreased in spores compared to vegetative cells, and rapidly increased at the onset of dormancy breaking upon glucose addition. This cytoplasmic fluidization depended on glucose sensing via the cAMP-PKA pathway. PKA activation led to trehalose degradation through trehalase Ntp1, thereby increasing particle mobility as the amount of trehalose decreased. In contrast, the rapid cytoplasmic fluidization did not require de novo protein synthesis, cytoskeletal dynamics, or cell volume increase. Furthermore, the measurement of diffusion coefficients with tracer particles of different sizes suggests that the spore cytoplasm impedes the movement of larger protein complexes (40-150 nm) such as ribosomes, while allowing free diffusion of smaller molecules (-3 nm) such as second messengers and signaling proteins. Our experiments have thus uncovered a series of signaling events that enable cells to quickly fluidize the cytoplasm at the onset of dormancy breaking.

    DOI: 10.1101/2023.09.27.559686

  8. Live-cell imaging provides direct evidence for a threshold in CDK activity at the G2/M transition

    Hironori Sugiyama, Yuhei Goto, Yohei Kondo, Damien Coudreuse, Kazuhiro Aoki

        2023年3月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    Cyclin-dependent kinase (CDK) plays an essential role in determining the temporal ordering of the cell cycle phases. However, despite significant progress in studying regulators of CDK, it remains elusive how they coordinately affect CDK activity at the single-cell level and how CDK controls the temporal order of cell cycle events. This could be due to the lack of tools to monitor CDK activity in living cells. Here, we elucidate the dynamics of CDK activity in fission yeast and mammalian cells by using a newly developed CDK activity biosensor, Eevee-spCDK, based on Forster Resonance Energy Transfer (FRET). Taking advantage of this system, we unravel the profile of CDK activity in vegetatively growing S. pombe cells. Thus, we detect a transient increase in S phase followed by a gradual increment during G2 phase. CDK activity then reaches its maximum in early M phase and rapidly decreases at mitotic exit. During G2 phase, CDK activity exhibits a biphasic pattern, i.e., an early slow increase and a late fast rise prior to the G2/M phase transition, as predicted from mathematical studies. Remarkably, although CDK activity does not necessarily correlate with cyclin levels, we find that it converges to the same level around mitotic onset in several mutant backgrounds, including pom1Δ cells and wee1 or cdc25 overexpressing cells. These data provide the first direct evidence that cells enter M phase when CDK activity reaches a high threshold, consistent with the quantitative model of cell cycle progression in fission yeast.

    DOI: 10.1101/2023.03.26.534249

  9. Quantitative live-cell imaging of GPCR downstream signaling dynamics. 査読有り 国際誌

    Ryosuke Tany, Yuhei Goto, Yohei Kondo, Kazuhiro Aoki

    The Biochemical journal   479 巻 ( 8 ) 頁: 883 - 900   2022年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    G-protein-coupled receptors (GPCRs) play an important role in sensing various extracellular stimuli, such as neurotransmitters, hormones, and tastants, and transducing the input information into the cell. While the human genome encodes more than 800 GPCR genes, only four Gα-proteins (Gαs, Gαi/o, Gαq/11, and Gα12/13) are known to couple with GPCRs. It remains unclear how such divergent GPCR information is translated into the downstream G-protein signaling dynamics. To answer this question, we report a live-cell fluorescence imaging system for monitoring GPCR downstream signaling dynamics. Genetically encoded biosensors for cAMP, Ca2+, RhoA, and ERK were selected as markers for GPCR downstream signaling, and were stably expressed in HeLa cells. GPCR was further transiently overexpressed in the cells. As a proof-of-concept, we visualized GPCR signaling dynamics of five dopamine receptors and 12 serotonin receptors, and found heterogeneity between GPCRs and between cells. Even when the same Gα proteins were known to be coupled, the patterns of dynamics in GPCR downstream signaling, including the signal strength and duration, were substantially distinct among GPCRs. These results suggest the importance of dynamical encoding in GPCR signaling.

    DOI: 10.1042/BCJ20220021

    PubMed

  10. LIM Tracker: a software package for cell tracking and analysis with advanced interactivity 査読有り 国際誌

    Hideya Aragaki, Katsunori Ogoh, Yohei Kondo, Kazuhiro Aoki

    Scientific Reports   12 巻 ( 1 ) 頁: 2702 - 2702   2022年2月

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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:Springer Science and Business Media LLC  

    <title>Abstract</title>Cell tracking is one of the most critical tools for time-lapse image analysis to observe cell behavior and cell lineages over a long period of time. However, the accompanying graphical user interfaces are often difficult to use and do not incorporate seamless manual correction, data analysis tools, or simple training set design tools if it is machine learning based. In this paper, we introduce our cell tracking software “LIM Tracker”. This software has a conventional tracking function consisting of recognition processing and link processing, a sequential search-type tracking function based on pattern matching, and a manual tracking function. LIM Tracker enables the seamless use of these functions. In addition, the system incorporates a highly interactive and interlocking data visualization method, which displays analysis result in real time, making it possible to flexibly correct the data and reduce the burden of tracking work. Moreover, recognition functions with deep learning (DL) are also available, which can be used for a wide range of targets including stain-free images. LIM Tracker allows researchers to track living objects with good usability and high versatility for various targets. We present a tracking case study based on fluorescence microscopy images (NRK-52E/EKAREV-NLS cells or MCF-10A/H2B-iRFP-P2A-mScarlet-I-hGem-P2A-PIP-NLS-mNeonGreen cells) and phase contrast microscopy images (Glioblastoma-astrocytoma U373 cells). LIM Tracker is implemented as a plugin for ImageJ/Fiji. The software can be downloaded from <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/LIMT34/LIM-Tracker">https://github.com/LIMT34/LIM-Tracker</ext-link>.

    DOI: 10.1038/s41598-022-06269-6

    PubMed

    その他リンク: https://www.nature.com/articles/s41598-022-06269-6

  11. Classification and Analysis of Liverwort Sperm by Integration-Net.

    Haruki Fujii, Naoki Minamino, Takashi Ueda, Yohei Kondo, Kazuhiro Hotta

    Proceedings of the 17th International Joint Conference on Computer Vision, Imaging and Computer Graphics Theory and Applications     頁: 699 - 705   2022年

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    掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:SCITEPRESS  

    DOI: 10.5220/0010915700003124

    その他リンク: https://dblp.uni-trier.de/db/conf/visapp/visapp2022-1.html#FujiiMUKH22

  12. Near-infrared imaging in fission yeast using a genetically encoded phycocyanobilin biosynthesis system

    Keiichiro Sakai, Yohei Kondo, Hiroyoshi Fujioka, Mako Kamiya, Kazuhiro Aoki, Yuhei Goto

    Journal of Cell Science   134 巻 ( 24 )   2021年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:The Company of Biologists  

    <title>ABSTRACT</title>
    Near-infrared fluorescent protein (iRFP) is a bright and stable fluorescent protein with near-infrared excitation and emission maxima. Unlike the other conventional fluorescent proteins, iRFP requires biliverdin (BV) as a chromophore. Here, we report that phycocyanobilin (PCB) functions as a brighter chromophore for iRFP than BV, and that biosynthesis of PCB allows live-cell imaging with iRFP in the fission yeast Schizosaccharomyces pombe. We initially found that fission yeast cells did not produce BV and therefore did not show any iRFP fluorescence. The brightness of iRFP–PCB was higher than that of iRFP–BV both in vitro and in fission yeast. We introduced SynPCB2.1, a PCB biosynthesis system, into fission yeast, resulting in the brightest iRFP fluorescence. To make iRFP readily available in fission yeast, we developed an endogenous gene tagging system with iRFP and all-in-one integration plasmids carrying the iRFP-fused marker proteins together with SynPCB2.1. These tools not only enable the easy use of multiplexed live-cell imaging in fission yeast with a broader color palette, but also open the door to new opportunities for near-infrared fluorescence imaging in a wider range of living organisms.


    This article has an associated First Person interview with the first author of the paper.

    DOI: 10.1242/jcs.259315

    その他リンク: https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.259315/2125216/jcs259315.pdf

  13. Optogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis 国際誌

    Kei Yamamoto, Haruko Miura, Motohiko Ishida, Yusuke Mii, Noriyuki Kinoshita, Shinji Takada, Naoto Ueno, Satoshi Sawai, Yohei Kondo, Kazuhiro Aoki

    Nature Communications   12 巻 ( 1 ) 頁: 7145 - 7145   2021年12月

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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:Springer Science and Business Media {LLC}  

    <jats:title>Abstract</jats:title><jats:p>Actomyosin contractility generated cooperatively by nonmuscle myosin II and actin filaments plays essential roles in a wide range of biological processes, such as cell motility, cytokinesis, and tissue morphogenesis. However, subcellular dynamics of actomyosin contractility underlying such processes remains elusive. Here, we demonstrate an optogenetic method to induce relaxation of actomyosin contractility at the subcellular level. The system, named OptoMYPT, combines a protein phosphatase 1c (PP1c)-binding domain of MYPT1 with an optogenetic dimerizer, so that it allows light-dependent recruitment of endogenous PP1c to the plasma membrane. Blue-light illumination is sufficient to induce dephosphorylation of myosin regulatory light chains and a decrease in actomyosin contractile force in mammalian cells and <jats:italic>Xenopus</jats:italic> embryos. The OptoMYPT system is further employed to understand the mechanics of actomyosin-based cortical tension and contractile ring tension during cytokinesis. We find that the relaxation of cortical tension at both poles by OptoMYPT accelerated the furrow ingression rate, revealing that the cortical tension substantially antagonizes constriction of the cleavage furrow. Based on these results, the OptoMYPT system provides opportunities to understand cellular and tissue mechanics.</jats:p>

    DOI: 10.1038/s41467-021-27458-3

    DOI: 10.1101/2021.04.19.440549

    PubMed

  14. Shedding light on developmental ERK signaling with genetically encoded biosensors

    Akinobu Nakamura, Yuhei Goto, Yohei Kondo, Kazuhiro Aoki

    Development   148 巻 ( 18 )   2021年9月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:The Company of Biologists  

    <title>ABSTRACT</title>
    The extracellular signal-regulated kinase (ERK) pathway governs cell proliferation, differentiation and migration, and therefore plays key roles in various developmental and regenerative processes. Recent advances in genetically encoded fluorescent biosensors have unveiled hitherto unrecognized ERK activation dynamics in space and time and their functional importance mainly in cultured cells. However, ERK dynamics during embryonic development have still only been visualized in limited numbers of model organisms, and we are far from a sufficient understanding of the roles played by developmental ERK dynamics. In this Review, we first provide an overview of the biosensors used for visualization of ERK activity in live cells. Second, we highlight the applications of the biosensors to developmental studies of model organisms and discuss the current understanding of how ERK dynamics are encoded and decoded for cell fate decision-making.

    DOI: 10.1242/dev.199767

  15. 【生物物理学の進歩-生命現象の定量的理解へ向けて】細胞レベル 情報理論による真核細胞の情報伝達機構の解析

    近藤 洋平, 青木 一洋

    生体の科学   72 巻 ( 3 ) 頁: 223 - 228   2021年6月

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    記述言語:日本語   出版者・発行元:(公財)金原一郎記念医学医療振興財団  

    <文献概要>細胞内情報伝達系の応答において,分子活性の時間的な変動や細胞内・個体内での分子局在の空間的な分布が重要であることがわかっている。しかし,このような複雑な応答と細胞外部環境との関係をいかに特徴づければよいだろうか。素朴に言えば,「時系列や空間分布に拡張された相関係数」のようなものが必要になるであろう。本稿では,情報理論を応用して前述の問題に対処しようとする近年の試みについて概観する。

  16. Visualization and manipulation of intracellular signaling 国際誌

    Goto, Y., Kondo, Y., Aoki, K.

    Advances in Experimental Medicine and Biology   1293 巻   頁: 225 - 234   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cells respond to a wide range of extracellular stimuli, and process the input information through an intracellular signaling system comprised of biochemical and biophysical reactions, including enzymatic and protein-protein interactions. It is essential to understand the molecular mechanisms underlying intracellular signal transduction in order to clarify not only physiological cellular functions but also pathological processes such as tumorigenesis. Fluorescent proteins have revolutionized the field of life science, and brought the study of intracellular signaling to the single-cell and subcellular levels. Much effort has been devoted to developing genetically encoded fluorescent biosensors based on fluorescent proteins, which enable us to visualize the spatiotemporal dynamics of cell signaling. In addition, optogenetic techniques for controlling intracellular signal transduction systems have been developed and applied in recent years by regulating intracellular signaling in a light-dependent manner. Here, we outline the principles of biosensors for probing intracellular signaling and the optogenetic tools for manipulating them.

    DOI: 10.1007/978-981-15-8763-4_13

    Scopus

    PubMed

  17. Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue 国際誌

    Asakura, Y., Kondo, Y., Aoki, K., Naoki, H.

    Scientific Reports   11 巻 ( 1 ) 頁: 4069 - 4069   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Collective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.

    DOI: 10.1038/s41598-021-83396-6

    Scopus

    PubMed

  18. Leaf form diversification in an heirloom tomato results from alterations in two different HOMEOBOX genes

    Hokuto Nakayama, Steven D. Rowland, Zizhang Cheng, Kristina Zumstein, Julie Kang, Yohei Kondo, Neelima R. Sinha

    Current Biology     2020年9月

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    出版者・発行元:Cold Spring Harbor Laboratory  

    <title>Abstract</title>Domesticated plants and animals display tremendous diversity in various phenotypic traits and often this diversity is seen within the same species. Tomato (<italic>Solanum lycopersicum</italic>; Solanaceae) cultivars show wide variation in leaf morphology, but the influence of breeding efforts in sculpting this diversity is not known. Here, we demonstrate that a single nucleotide deletion in the homeobox motif of <italic>BIPINNATA</italic>, which is a <italic>BEL-LIKE HOMEODOMAIN</italic> gene, led to a highly complex leaf phenotype in an heirloom tomato, Silvery Fir Tree (SiFT). Additionally, a comparative gene network analysis revealed that reduced expression of the ortholog of <italic>WUSCHEL RELATED HOMEOBOX 1</italic> is also important for the narrow leaflet phenotype seen in SiFT. Phylogenetic and comparative genome analysis using whole-genome sequencing data suggests that the <italic>bip</italic> mutation in SiFT is likely a <italic>de novo</italic> mutation, instead of standing genetic variation. These results provide new insights into natural variation in phenotypic traits introduced into crops during improvement processes after domestication.

    DOI: 10.1101/2020.09.08.287011

  19. Improvement of phycocyanobilin synthesis for genetically encoded phytochrome-based optogenetics

    Uda, Y., Miura, H., Goto, Y., Yamamoto, K., Mii, Y., Kondo, Y., Takada, S., Aoki, K.

    ACS Chemical Biology   15 巻 ( 11 )   2020年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:American Chemical Society (ACS)  

    DOI: 10.1021/acschembio.0c00477

    Scopus

  20. Single-cell quantification of the concentrations and dissociation constants of endogenous proteins 査読有り

    Komatsubara, A.T., Goto, Y., Kondo, Y., Matsuda, M., Aoki, K.

    Journal of Biological Chemistry   294 巻 ( 15 ) 頁: 6062 - 6072   2019年

     詳細を見る

    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1074/jbc.RA119.007685

    Scopus

    PubMed

  21. Inverse tissue mechanics of cell monolayer expansion 査読有り

    Kondo, Y., Aoki, K., Ishii, S.

    PLoS Computational Biology   14 巻 ( 3 ) 頁: e1006029   2018年

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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:Public Library of Science ({PLoS})  

    Living tissues undergo deformation during morphogenesis. In this process, cells generate mechanical forces that drive the coordinated cell motion and shape changes. Recent advances in experimental and theoretical techniques have enabled in situ measurement of the mechanical forces, but the characterization of mechanical properties that determine how these forces quantitatively affect tissue deformation remains challenging, and this represents a major obstacle for the complete understanding of morphogenesis. Here, we proposed a non-invasive reverse-engineering approach for the estimation of the mechanical properties, by combining tissue mechanics modeling and statistical machine learning. Our strategy is to model the tissue as a continuum mechanical system and to use passive observations of spontaneous tissue deformation and force fields to statistically estimate the model parameters. This method was applied to the analysis of the collective migration of Madin-Darby canine kidney cells, and the tissue flow and force were simultaneously observed by the phase contrast imaging and traction force microscopy. We found that our monolayer elastic model, whose elastic moduli were reverse-engineered, enabled a long-term forecast of the traction force fields when given the tissue flow fields, indicating that the elasticity contributes to the evolution of the tissue stress. Furthermore, we investigated the tissues in which myosin was inhibited by blebbistatin treatment, and observed a several-fold reduction in the elastic moduli. The obtained results validate our framework, which paves the way to the estimation of mechanical properties of living tissues during morphogenesis.

    DOI: 10.1371/journal.pcbi.1006029

    Scopus

    PubMed

  22. Inferring a nonlinear biochemical network model from a heterogeneous single-cell time course data 査読有り

    Shindo, Y., Kondo, Y., Sako, Y.

    Scientific Reports   8 巻 ( 1 ) 頁: 6790   2018年

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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  

    Mathematical modeling and analysis of biochemical reaction networks are key routines in computational systems biology and biophysics
    however, it remains difficult to choose the most valid model. Here, we propose a computational framework for data-driven and systematic inference of a nonlinear biochemical network model. The framework is based on the expectation-maximization algorithm combined with particle smoother and sparse regularization techniques. In this method, a "redundant" model consisting of an excessive number of nodes and regulatory paths is iteratively updated by eliminating unnecessary paths, resulting in an inference of the most likely model. Using artificial single-cell time-course data showing heterogeneous oscillatory behaviors, we demonstrated that this algorithm successfully inferred the true network without any prior knowledge of network topology or parameter values. Furthermore, we showed that both the regulatory paths among nodes and the optimal number of nodes in the network could be systematically determined. The method presented in this study provides a general framework for inferring a nonlinear biochemical network model from heterogeneous single-cell time-course data.

    DOI: 10.1038/s41598-018-25064-w

    Scopus

    PubMed

  23. Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death 査読有り 国際誌

    Miura, H., Kondo, Y., Matsuda, M., Aoki, K.

    Cell Reports   24 巻 ( 10 ) 頁: 2658 - 2668   2018年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are important players in cell-fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in inflammatory and stress responses. However, it is unknown how this crosstalk affects signaling dynamics, cell-to-cell variation, and cellular responses at the single-cell level. We established a multiplexed live-cell imaging system based on kinase translocation reporters to simultaneously monitor JNK and p38 activities with high specificity and sensitivity at single-cell resolution. Various stresses activated JNK and p38 with various dynamics. In all cases, p38 suppressed JNK activity in a cross-inhibitory manner. We demonstrate that p38 antagonizes JNK through both transcriptional and post-translational mechanisms. This cross-inhibition generates cellular heterogeneity in JNK activity after stress exposure. Our data indicate that this heterogeneity in JNK activity plays a role in fractional killing in response to UV stress.

    DOI: 10.1016/j.celrep.2018.08.020

    Scopus

    PubMed

  24. Sparse Bayesian linear regression with latent masking variables 査読有り

    Kondo, Y., Hayashi, K., Maeda, S.-I.

    Neurocomputing   258 巻   頁: 3 - 12   2017年

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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:Elsevier {BV}  

    Extracting a small number of relevant features for the task, i.e., feature selection, is often a crucial step in supervised learning problems. Sparse linear regression provides a fast and convenient option for feature selection, where regularization facilitates reducing the weight parameters of irrelevant features. However, the regularization also induces undesirable shrinkage in the weights of relevant features.
    Here, we propose Bayesian masking (BM) in order to resolve the trade-off problem between sparsity and shrinkage. Our strategy is not to directly impose any regularization on the weights; instead, BM introduces binary latent variables, called masking variables, into a regression model to keep the sparsity; each feature and sample has a binary variable whose value determines if the feature is masked or not at the sample. We derive a variational Bayesian inference algorithm for the augmented model based on the factorized information criterion (FIC), a recently-proposed asymptotic approximation of the marginal log-likelihood. We analyze the one-dimensional estimators of Lasso, automatic relevance determination (ARD), and BM, and thus show the superiority of BM in terms of the sparsity-shrinkage trade-off. Finally, we confirm our theoretical analyses through experiments and, demonstrate that BM achieves higher feature selection accuracy compared with Lasso and ARD. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.neucom.2016.12.080

    Web of Science

    Scopus

  25. Propagating Wave of ERK Activation Orients Collective Cell Migration 査読有り

    Aoki, K., Kondo, Y., Naoki, H., Hiratsuka, T., Itoh, R.E., Matsuda, M.

    Developmental Cell   43 巻 ( 3 ) 頁: 305 - +   2017年

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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:CELL PRESS  

    The biophysical framework of collective cell migration has been extensively investigated in recent years; however, it remains elusive how chemical inputs from neighboring cells are integrated to coordinate the collective movement. Here, we provide evidence that propagation waves of extracellular signal-related kinase (ERK) mitogen-activated protein kinase activation determine the direction of the collective cell migration. A wound-healing assay of Mardin-Darby canine kidney (MDCK) epithelial cells revealed two distinct types of ERK activation wave, a "tidal wave'' from the wound, and a self-organized "spontaneous wave'' in regions distant from the wound. In both cases, MDCK cells collectively migrated against the direction of the ERK activation wave. The inhibition of ERK activation propagation suppressed collective cell migration. An ERK activation wave spatiotemporally controlled actomyosin contraction and cell density. Furthermore, an optogenetic ERK activation wave reproduced the collective cell migration. These data provide new mechanistic insight into how cells sense the direction of collective cell migration.

    DOI: 10.1016/j.devcel.2017.10.016

    Web of Science

    Scopus

    PubMed

  26. Fold-change detection and scale invariance of cell–cell signaling in social amoeba 査読有り

    Keita Kamino, Yohei Kondo, Akihiko Nakajima, Mai Honda-Kitahara, Kunihiko Kaneko, Satoshi Sawai

    Proceedings of the National Academy of Sciences   114 巻 ( 21 ) 頁: E4149 - E4157   2017年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Proceedings of the National Academy of Sciences  

    DOI: 10.1073/pnas.1702181114

    Web of Science

    Scopus

  27. Rescaling of spatio-temporal sensing in eukaryotic chemotaxis 査読有り

    Kamino, K., Kondo, Y.

    PLoS ONE   11 巻 ( 10 ) 頁: e0164674   2016年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Public Library of Science ({PLoS})  

    Eukaryotic cells respond to a chemoattractant gradient by forming intracellular gradients of signaling molecules that reflect the extracellular chemical gradient D an ability called directional sensing. Quantitative experiments have revealed two characteristic input-output relations of the system: First, in a static chemoattractant gradient, the shapes of the intracellular gradients of the signaling molecules are determined by the relative steepness, rather than the absolute concentration, of the chemoattractant gradient along the cell body. Second, upon a spatially homogeneous temporal increase in the input stimulus, the intracellular signaling molecules are transiently activated such that the response magnitudes are dependent on fold changes of the stimulus, not on absolute levels. However, the underlying mechanism that endows the system with these response properties remains elusive. Here, by adopting a widely used modeling framework of directional sensing, local excitation and global inhibition (LEGI), we propose a hypothesis that the two rescaling behaviors stem from a single design principle, namely, invariance of the governing equations to a scale transformation of the input level. Analyses of the LEGI-based model reveal that the invariance can be divided into two parts, each of which is responsible for the respective response properties. Our hypothesis leads to an experimentally testable prediction that a system with the invariance detects relative steepness even in dynamic gradient stimuli as well as in static gradients. Furthermore, we show that the relation between the response properties and the scale invariance is general in that it can be implemented by models with different network topologies.

    DOI: 10.1371/journal.pone.0164674

    Web of Science

    Scopus

    PubMed

    J-GLOBAL

  28. Bayesian Masking: Sparse Bayesian Estimation with Weaker Shrinkage Bias 査読有り

    近藤 洋平

    The 7th Asian Conference on Machine Learning (ACML)     頁: 49 - 64   2015年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

    その他リンク: https://dblp.uni-trier.de/rec/conf/acml/2015

  29. Identifying dynamical systems with bifurcations from noisy partial observation 査読有り

    Kondo, Y., Kaneko, K., Ishihara, S.

    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics   87 巻 ( 4 )   2013年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Physical Society ({APS})  

    We propose a statistical machine-learning approach to derive low-dimensional models by integrating noisy time-series data from partial observation of high-dimensional systems, aiming to utilize quantitative data on biological phenomena in the cell. In particular, the method estimates a model from data at different values of a bifurcation parameter in order to characterize biological functions as bifurcation types that are insensitive to system details and experimental errors. The method is tested using artificial data generated from two cell-cycle control system models that exhibit different bifurcations and the learned systems are shown to robustly inherit the bifurcation types. DOI: 10.1103/PhysRevE.87.042716

    DOI: 10.1103/PhysRevE.87.042716

    Web of Science

    Scopus

  30. Growth states of catalytic reaction networks exhibiting energy metabolism 査読有り

    Kondo, Y., Kaneko, K.

    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics   84 巻 ( 1 )   2011年

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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:AMER PHYSICAL SOC  

    All cells derive nutrition by absorbing some chemical and energy resources from the environment; these resources are used by the cells to reproduce the chemicals within them, which in turn leads to an increase in their volume. In this study we introduce a protocell model exhibiting catalytic reaction dynamics, energy metabolism, and cell growth. Results of extensive simulations of this model show the existence of four phases with regard to the rates of both the influx of resources and cell growth. These phases include an active phase with high influx and high growth rates, an inefficient phase with high influx but low growth rates, a quasistatic phase with low influx and low growth rates, and a death phase with negative growth rate. A mean field model well explains the transition among these phases as bifurcations. The statistical distribution of the active phase is characterized by a power law, and that of the inefficient phase is characterized by a nearly equilibrium distribution. We also discuss the relevance of the results of this study to distinct states in the existing cells.

    DOI: 10.1103/PhysRevE.84.011927

    Web of Science

    Scopus

▼全件表示

MISC 4

  1. ミオシンの光操作で明らかになった細胞質分裂における両極アクトミオシンの寄与

    山本啓, 近藤洋平  

    生物物理62 巻 ( 5 ) 頁: 285 - 287   2022年10月

     詳細を見る

  2. 多細胞集団の力学への機械学習アプローチ

    近藤洋平, 杉村薫  

    実験医学増刊38 巻 ( 20 ) 頁: 161 - 168   2020年12月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(その他)  

  3. 動く組織の力学特性を測る

    近藤洋平  

    生体の科学70 巻 ( 4 ) 頁: 284 - 289   2019年8月

     詳細を見る

    担当区分:筆頭著者  

  4. スケール不変な細胞間シグナリング 招待有り

    神野圭太, 近藤洋平, 澤井哲  

    生物物理58 巻 ( 6 ) 頁: 316 - 318   2018年12月

     詳細を見る

    記述言語:日本語  

    DOI: 10.2142/biophys.58.316

科研費 4

  1. ゼニゴケ油体をモデルとしたオルガネラ周期の証明と中心因子の同定

    研究課題/研究課題番号:19H05675  2019年6月 - 2024年3月

    日本学術振興会  科学研究費助成事業 新学術領域研究(研究領域提案型)  新学術領域研究(研究領域提案型)

    上田 貴志, 近藤 洋平, 河内 孝之, 金澤 建彦, 近藤 洋平, 河内 孝之, 金澤 建彦

      詳細を見る

    担当区分:研究分担者 

    油体周期仮説では、細胞膜期と油体期が相互に転換することを想定している。細胞膜期と油体期ではトランスクリプトームが転換すると考えられることから、2021年度においても引き続きその実証のための実験を進めた。油体周期の周期長や葉状体内での油体周期の同調の程度についての知見を得るため、油体期に転写されるMpSYP12Bのプロモーターの制御下でPEST配列を連結したELucを発現し、発光を検出した。その結果、発光が周期的に増強と減弱を繰り返す様子が観察されたが、その周期は2周期程度しか持続せず、これが油体周期の本来の性質であるのかどうか疑問が残った。そこで、実験条件を検討したところ、発光を検出するための暗黒条件では、油体形成が停止することが見いだされた。この問題を解決するため、所属研究所の光学解析室の協力を得て間欠照明装置の開発を進め、非撮影時には照明を当てつつ長時間ゼニゴケを培養しながらライブイメージング観察を行うことが可能になった。
    これと平行して、細胞膜と油体膜を蛍光タンパク質で可視化した形質転換体を長時間観察することも試みた。前年度の解析により、MpSYP12Bにより油体膜が認識できるようになる約12時間前に油体母細胞が不等分裂し、娘細胞のうちの小さい細胞に油体が形成される様子が観察されていたが、この現象も照明を当てることで長時間観察できるようになることが明らかになった。今後は観察の効率が向上するものと期待される。
    油体の形態が異常になる変異体の解析も進めている。油体の形態や分布に異常を示す個体をスクリーニングし、これまでに複数の候補を得ている。そのうちの一つについて詳細な解析を進め、ゴルジ体に局在する被覆複合体の構成因子、MpSEC28の変異が原因で油体形態が異常になっていることを明らかにした。現在この変異体の表現型やMpSEC28の機能のさらなる解析を進めている。

  2. 遺伝子発現ゆらぎの分散と多峰性が進化速度におよぼす影響の測定

    研究課題/研究課題番号:19K16207  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 若手研究  若手研究

    近藤 洋平

      詳細を見る

    担当区分:研究代表者 

    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    (1)人工遺伝子回路による薬剤耐性遺伝子発現の制御:多剤排出トランスポーターbfr1を野生株からクローニングし、蛍光レポーターを付加して分裂酵母染色体に組み込んだ。このbfr1の発現を定量的に制御するためにTet発現誘導システムの利用を予定していたが、より高い発現量を実現できるエストラジオール発現誘導システムを代わりに用いた。抗生物質としてブレフェルジンAとシクロヘキシミドを使い、組み込んだbfr1が実際に薬剤耐性を強化することを確認した。上記のシステムを組み込む細胞株については、薬剤スクリーニングのために作出され内在性の薬剤耐性システムを欠いているSAK879を利用することとした。SAK879ではbfr1発現量による増殖速度の違いが大きいため、次年度に実施する進化実験においてデータのシグナル-ノイズ比が改善し、また実験期間も短縮できると期待される。
    (2)プロモーターへの変異導入による発現ゆらぎの増強と抑制:PCRを用いたランダム変異導入によって、プロモーターPadh1の変異ライブラリーを作成した。変異プロモーターのスクリーニングを実施し、発現ゆらぎが野生型と異なるプロモーター候補を得ている。
    (3)一細胞増殖動態の測定:細胞の位置を固定し、長時間の観察を可能にする微小流体デバイスを利用して、一細胞レベルでの耐性遺伝子発現量と増殖速度を測定し、正の相関を確認した。
    <BR>
    (1)、(2)、および(3)によって、本研究の目的である「遺伝子発現ゆらぎの確率分布形状が進化速度におよぼす影響を進化実験によって測定する」ための準備が整ったといえる。

  3. 時空間モデルの推定と「予測不可能性の定量」にもとづくシンギュラリティ細胞の同定

    研究課題/研究課題番号:19H05438  2019年4月 - 2021年3月

    科学研究費助成事業  新学術領域研究(研究領域提案型)

    近藤 洋平

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    担当区分:研究代表者 

    配分額:5200000円 ( 直接経費:4000000円 、 間接経費:1200000円 )

    本研究が参加する新学術領域は、シンギュラリティ細胞、すなわち集団中で特異な振る舞いをする細胞が、臓器や個体といったシステム全体の運命を決定するという現象の解明を目指している。そこで本研究では、生細胞イメージング動画データ内のシンギュラリティ細胞を自動的に発見する手法を開発する。より具体的には、データから画像解析および時系列モデルの学習によって細胞の振る舞いに対する予測モデルを構成し、それを各細胞へ適用することで「どの程度平均から外れた振る舞いをするか」を定量化する。本手法は、上皮培養細胞の創傷治癒過程というよく研究された系を用いてその有効性を検証する。
    MAPキナーゼERK活性の時空間動態が引き起こす細胞集団運動が、創傷治癒やがんの浸潤との関連から、近年注目を集めている。この現象は、組織力学とシグナル伝達系の間でフィードバックループが構成されることから発生していると考えられており、その力学-化学相互作用について様々な数理モデルが提案されている。しかし、それらのモデルは集団運動の組織スケールでの観察を定性的に再現するものの、仮定されている細胞生物学的メカニズムが現実と対応しているかについての検証に乏しい。その結果、異なる機構を仮定し た複数のモデルの支持者の間で論争が発生している。我々は最も直接的な解決手段として、 一細胞レベルでモデルと実際の挙動を定量的に比較することを試みたが、各々の細胞挙動が極度にランダムであるため、モデル選択が困難であると判明した。そこでdiscrete-to-continuum極限をとる手続きによって一細胞レベルの分解能を持ったモデルを組織スケールのモデルへと変換し、その粗視化されたスケールにおいてモデルと実験結果の比較を実施する手続きを提案した。元の細胞スケールモデルと我々が得た組織スケールのモデルの対応を、数値計算によって示すことができた。組織再生過程におけるERK活性の細胞間伝播はマウスやゼブラフィッシュなどの様々な脊椎動物において広く観察されており、普遍的なメカニズムの存在が示唆されている。我々の成果はその解明に役立つと期待できる。
    令和2年度が最終年度であるため、記入しない。
    令和2年度が最終年度であるため、記入しない。

  4. 集団運動する細胞組織の力学特性の推定

    研究課題/研究課題番号:26840077  2014年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    近藤 洋平

      詳細を見る

    担当区分:研究代表者 

    配分額:1690000円 ( 直接経費:1300000円 、 間接経費:390000円 )

    動物の体が形づくられるとき、多数の細胞が協同して力を発し自らを変形させる。その際、生体組織自身の硬さ・粘さといった力学的性質が適切に制御されていることが必要である。そういった物理パラメータを見積もるため、組織を圧縮したり切断したりといった外的操作によって変形させて力学的応答を観測するという手法がしばしば用いられる。しかし、そのような外力は自発的な形づくりの過程を阻害してしまう。この問題を回避するため我々は、細胞組織のマルチフィジックスモデルを構築し、そのパラメータを顕微鏡動画データにもとづき統計学的に推定するという手法を提案し、培養細胞シートを用いてその有効性を示した。