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Elucidating the mechanism underlying the mesenchymal polarization of the trachea through Wnt signaling

Research Project

Project/Area Number 19K16156
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Kishimoto Keishi  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 (70700029)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords気管 / 極性化 / 間充織 / Wnt / 上皮 / 幹細胞 / オルガノイド / 細胞極性 / Wnt signaling / マウス気管
Outline of Research at the Start

臓器のかたちは、細胞の振る舞いや細胞間の協調的な運動によって決定づけられる。細胞の極性化は、細胞や組織に方向性や協調性を与えるイベントであり、臓器が正しい三次元構造を作るために必須の過程である。
申請者は、間充織細胞が上皮組織方向に極性を同調させながら、マウス気管管腔の長さを決定することを発見した。これらの結果は、臓器の形態形成における間充織細胞の極性化の重要性を示している。本研究計画では、気管発生における間充織細胞の極性化を制御する上皮―間充織相互作用を理解することを目的とする。さらに、幹細胞を用いた再構成論的アプローチにより、ヒト気管発生における間充織細胞の極性化過程の可視化にも取り組む。

Outline of Final Research Achievements

In this study, we attempted to explore the Wnt-related genes which are expected to be involved in mesenchymal polarization of the trachea. scRNA-seq transcriptomics and its validation with in situ hybidization have identified several Wnt signaling components during mesenchymal polarization. We also tried to establish the system in which the process of mesenchymal polarization can be analyzed in vitro. We have succeeded in generating tracheal mesenchyme from human/mouse embryonic stem cells. We are currently combining these mesenchyme with epithelial cells to recapitulate the process of tracheal mesenchymal polarization.

Academic Significance and Societal Importance of the Research Achievements

我々は先行研究において、気管が正しい長さと太さに成長するためには、間充織細胞の極性化が必要であることを見出した。一方、これまでの当該分野の研究の多くは上皮細胞に焦点をあっており、間充織組織の発生についてはあまり研究されていなかった。本研究では、呼吸器間充織細胞をヒト幹細胞から作成することを世界に先駆けて成功した。これらの細胞を上皮細胞と混合培養することで、ヒト臓器の形成過程を培養皿上で再構築する技術の確立に繋がる。これらの技術はヒト臓器の正常な形成機構の解明・病態の理解につながると期待される。

Report

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

    (10 results)

All 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] CincinnatiChildrensHospitalMedicalCenter(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Cincinnati Children Hospital(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells2022

    • Author(s)
      Eicher Alexandra K.、Kechele Daniel O.、Sundaram Nambirajan、Berns H. Matthew、Poling Holly M.、Haines Lauren E.、Sanchez J. Guillermo、Kishimoto Keishi、Krishnamurthy Mansa、Han Lu、Zorn Aaron M.、Helmrath Michael A.、Wells James M.
    • Journal Title

      Cell Stem Cell

      Volume: 29 Issue: 1 Pages: 36-51.e6

    • DOI

      10.1016/j.stem.2021.10.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Directed differentiation of human pluripotent stem cells into diverse organ-specific mesenchyme of the digestive and respiratory systems.2022

    • Author(s)
      Keishi Kishimoto, Kentaro Iwasawa, Alice Sorel, Carlos Ferran-Heredia, Lu Han, Mitsuru Morimoto, James M Wells, Takanori Takebe and Aaron M Zorn
    • Journal Title

      nature protocols

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mammalian tracheal development and reconstruction: insights from <i>in vivo</i> and <i>in vitro</i> studies2021

    • Author(s)
      Kishimoto Keishi、Morimoto Mitsuru
    • Journal Title

      Development

      Volume: 148 Issue: 13

    • DOI

      10.1242/dev.198192

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single cell transcriptomics identifies a signaling network coordinating endoderm and mesoderm diversification during foregut organogenesis.2020

    • Author(s)
      Han L, Chaturvedi P, Kishimoto K, Koike H, Nasr T, Iwasawa K, Giesbrecht K, Witcher PC, Eicher A, Haines L, Lee Y, Shannon JM, Morimoto M, Wells JM, Takebe T, Zorn AM.
    • Journal Title

      Nature communications

      Volume: 11(1) Issue: 1 Pages: 4158-4158

    • DOI

      10.1038/s41467-020-17968-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells.2020

    • Author(s)
      Kishimoto K, Furukawa KT, Luz-Madrigal A, Yamaoka A, Matsuoka C, Habu M, Alev C, Zorn AM, Morimoto M.
    • Journal Title

      Nature communications

      Volume: 11(1) Issue: 1 Pages: 4159-4159

    • DOI

      10.1038/s41467-020-17969-w

    • NAID

      120006882430

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bidirectional Wnt signaling between endoderm and mesoderm confer tracheal identity in mouse and human2020

    • Author(s)
      Keishi Kishimoto, Kana T. Furukawa, Agustin Luz Madrigal, Akira Yamaoka, Chisa Matsuoka, Masanobu Habu, Cantas Alev, Aaron M. Zorn, Mitsuru Morimoto
    • Journal Title

      Biorxiv

      Volume: 756825 Pages: 1-31

    • DOI

      10.1101/758235

    • Related Report
      2019 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Single cell transcriptomics reveals a signaling roadmap coordinating endoderm and mesoderm diversification during foregut organogenesis2020

    • Author(s)
      Lu Han, Praneet Chaturvedi, Keishi Kishimoto, Hiroyuki Koike, Talia Nasr, Kentaro Iwasawa, Kirsten Giesbrecht, Phillip C Witcher, Alexandra Eicher, Lauren Haines, Yarim Lee, John M Shannon, Mitsuru Morimoto, James M Wells, Takanori Takebe, Aaron M Zorn
    • Journal Title

      Biorxiv

      Volume: 861781 Pages: 1-49

    • DOI

      10.1101/756825

    • Related Report
      2019 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Induction of organ specific splanchnic mesoderm from human embryonic stem cell2020

    • Author(s)
      Keishi Kishimoto
    • Organizer
      CLEAR consortium 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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