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Revealing the mechanism of mechanical regulation in minimal multi-cellular units of epithelial tissues

Research Project

Project/Area Number 19K16096
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43040:Biophysics-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Yamamoto Takaki  国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (30805338)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords生物物理 / 上皮組織 / メカノバイオロジー / 機械学習 / グラフニューラルネットワーク
Outline of Research at the Start

上皮細胞が隙間なく接着した細胞層である上皮組織は、多細胞生物の生命活動に不可欠であり、上皮組織の機能解明は生物学の重要な課題である。上皮組織は、細胞同士が互いに力を及ぼし合うことで、細胞間接着を維持しながら、動的に互いの位置関係を変化させ、生物学的機能を果たす。そのため、上皮組織の機能の理解のためには、上皮組織の動態を支配する、細胞間の力学機構を解明することが不可欠である。本研究では、上皮組織を構成するミニマルな多細胞ユニットである、3細胞で上皮構造を維持できる実験系を確立する。そして、この系を用いて、細胞間の力学が各細胞の状態を介した相互作用により、どのように制御されるかを定量的に解明する。

Outline of Final Research Achievements

In this research, we aimed to understand how the functions and structures of epithelial tissues, which are essential for multi-cellular organisms, are maintained. We revealed how the mechanical properties of epithelial cells affect the tissue-level dynamics using a mathematical model of epithelial tissues. Furthermore, we proposed a machine-learning framework which probes the cell-to-cell interaction rules from the live-image data of tissues. Using the framework, we identified cell-to-cell interaction rules in the mouse epidermis.

Academic Significance and Societal Importance of the Research Achievements

本研究では、上皮細胞の力学的性質の時間的なゆらぎが、上皮組織のダイナミクスに与える影響を理論的に調べ、これまで報告されていなかった上皮組織の性質を見つけることができ、多細胞組織に関する新たな生物物理学的な知見を得ることができた。また、本研究で開発した多細胞組織における細胞間の相互作用の推定手法は、様々な組織に対して適用可能であり、生物学の大きなテーマである細胞間相互作用の理解を推し進めるための一歩になった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Open Access: 6 results,  Peer Reviewed: 6 results) Presentation (11 results) (of which Int'l Joint Research: 6 results)

  • [Int'l Joint Research] Syracuse University/Yale University(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Syracuse university/University of Chicago/Emory university(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] シラキュース大学(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Non-monotonic fluidization generated by fluctuating edge tensions in confluent tissues2022

    • Author(s)
      Yamamoto Takaki、Sussman Daniel M.、Shibata Tatsuo、Manning M. Lisa
    • Journal Title

      Soft Matter

      Volume: 18 Issue: 11 Pages: 2168-2175

    • DOI

      10.1039/d0sm01559h

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Probing the rules of cell coordination in live tissues by interpretable machine learning based on graph neural networks2021

    • Author(s)
      Yamamoto Takaki、Cockburn Katie、Greco Valentina、Kawaguchi Kyogo
    • Journal Title

      bioRxiv

      Volume: 2021.06.23.449559

    • DOI

      10.1101/2021.06.23.449559

    • Related Report
      2021 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Tracheal motile cilia in mice require CAMSAP3 for the formation of central microtubule pair and coordinated beating2021

    • Author(s)
      Saito Hiroko、Matsukawa-Usami Fumiko、Fujimori Toshihiko、Kimura Toshiya、Ide Takahiro、Yamamoto Takaki、Shibata Tatsuo、Onoue Kenta、Okayama Satoko、Yonemura Shigenobu、Misaki Kazuyo、Soba Yurina、Kakui Yasutaka、Sato Masamitsu、Toya Mika、Takeichi Masatoshi
    • Journal Title

      Molecular Biology of the Cell

      Volume: 32 Issue: 20 Pages: ar12-ar12

    • DOI

      10.1091/mbc.e21-06-0303

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tracing the origin of hair follicle stem cells2021

    • Author(s)
      Morita Ritsuko、Sanzen Noriko、Sasaki Hiroko、Hayashi Tetsutaro、Umeda Mana、Yoshimura Mika、Yamamoto Takaki、Shibata Tatsuo、Abe Takaya、Kiyonari Hiroshi、Furuta Yasuhide、Nikaido Itoshi、Fujiwara Hironobu
    • Journal Title

      Nature

      Volume: 594 Issue: 7864 Pages: 547-552

    • DOI

      10.1038/s41586-021-03638-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell cycle-dependent active stress drives epithelia remodeling2021

    • Author(s)
      John Devany, Daniel M. Sussman, Takaki Yamamoto, M. Lisa Manning, Margaret L. Gardel
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: 118, 10 Issue: 10 Pages: 1-9

    • DOI

      10.1073/pnas.1917853118

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Non-monotonic fluidization generated by fluctuating edge tensions in confluent tissues2020

    • Author(s)
      Takaki Yamamoto, Daniel M. Sussman, Tatsuo Shibata, M. Lisa Manning
    • Journal Title

      arXiv

      Volume: 2008.13007

    • Related Report
      2020 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Collective cell migration of epithelial cells driven by chiral torque generation2020

    • Author(s)
      Yamamoto Takaki、Hiraiwa Tetsuya、Shibata Tatsuo
    • Journal Title

      Physical Review Research

      Volume: 2 Issue: 4 Pages: 043326-043326

    • DOI

      10.1103/physrevresearch.2.043326

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reorientation behavior in the helical motility of light-responsive spiral droplets2019

    • Author(s)
      Federico lancia, Takaki Yamamoto, Alexander Ryabchun, Tadatsugu Yamaguchi, Masaki Sano, Nathalie Katsonis
    • Journal Title

      Nature Communications

      Volume: 10(5238) Issue: 1

    • DOI

      10.1038/s41467-019-13201-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Collective cell migration of epithelial cells driven by chiral torque generation2019

    • Author(s)
      Takaki Yamamoto, Tetsuya Hiraiwa and Tatsuo Shibata
    • Journal Title

      arXiv

      Volume: 1909.02771

    • Related Report
      2019 Research-status Report
    • Open Access
  • [Presentation] グラフニューラルネットワークによる細胞間の時空間相互作用の推定2022

    • Author(s)
      山本尚貴
    • Organizer
      日本物理学会 第77回年次大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Graph-based machine learning reveals rules of spatiotemporal cell interactions in tissues2022

    • Author(s)
      Takaki Yamamoto
    • Organizer
      RIKEN BDR Symposium 2022 “Emergence in Biological Systems: Emergence in Biological Systems: Challenges to Bridging Hierarchies”
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Emergence of cell chirality from the spatial organization of actin and myosin cytoskeleton2022

    • Author(s)
      Tatsuo Shibata
    • Organizer
      RIKEN BDR Symposium 2022 “Emergence in Biological Systems: Emergence in Biological Systems: Challenges to Bridging Hierarchies”
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Collective cell migration of epithelial cells driven by chiral torque generation2021

    • Author(s)
      Takaki Yamamoto
    • Organizer
      EMBO Workshop Physics of living systems: From molecules to tissues
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Graph-based machine learning reveals rules of spatiotemporal cell interactions in tissues2021

    • Author(s)
      Takaki Yamamoto
    • Organizer
      RIKEN BDR Retreat 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Non-monotonic fluidization generated by fluctuating edge tensions in confluent tissues2021

    • Author(s)
      Takaki Yamamoto, Daniel M. Sussman, Tatsuo Shibata, M. Lisa Manning
    • Organizer
      RIKEN BDR symposium 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chirality-induced helical self-propulsion of chiral liquid crystal droplets2019

    • Author(s)
      Takaki Yamamoto
    • Organizer
      Gordon Research Seminar "Designing Mechanics and Dynamics in Soft Matter”
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Theoretical model of dynamics of epithelial cells with cellular chiral torque generation2019

    • Author(s)
      Takaki Yamamoto
    • Organizer
      Gordon Research Conference "Living and Non-Living Soft Matter on the Edge: Out of Equilibrium, Marginal, in Extreme Conditions and at Interfaces”
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] キラルな液晶液滴のマランゴニ効果駆動の回転運動とその流体場2019

    • Author(s)
      山本尚貴
    • Organizer
      日本物理学会 2019年秋季大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 細胞のキラリティを考慮した上皮細胞組織の運動モデル2019

    • Author(s)
      山本尚貴
    • Organizer
      日本物理学会 2019年秋季大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Theoretical model of dynamics of epithelial tissue with cellular chirality2019

    • Author(s)
      山本尚貴
    • Organizer
      第57回日本生物物理学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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