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Establishment of human airway organoid by understanding airway development in single-cell resolution

Research Project

Project/Area Number 20H03693
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Mitsuru Morimoto  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, チームリーダー (70544344)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords呼吸器 / 気道 / 発生学 / 幹細胞 / オルガノイド / 気管 / 発生 / 1細胞転写解析 / シングルセル解析 / 1細胞解析
Outline of Research at the Start

本研究はマウス胚の気道細胞の1細胞転写解析により、上皮4細胞種、間充織2細胞種の分化プロセスを完全マッピングすることで、気道発生原理を分子レベルで理解する。その知識を利用したヒトiPS/ES細胞からのヒト気道の再構成によるヒト気道発生機構の解明、最終的に上皮-間充織相互作用を検証できるヒト気道オルガノイドの開発を試みる。

Outline of Final Research Achievements

The study examined fetal mouse airway epithelium and mesenchymal tissue differentiation at a single-cell level via scRNA-seq. Key findings include early fate decisions in basal cells at E14.5, driven by TGFb upregulation and subsequent cell proliferation decrease. TGFb signaling induced differentiation, delayed in TGFb receptor-deficient epithelia. Injury studies revealed reversal of developmental dynamics in tissue regeneration. Additionally, distinct origins for tracheal cartilage and smooth muscle were identified. A protocol for inducing tracheal mesenchymal tissue from human ES cells was established. Further research focuses on optimizing co-culturing conditions with epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

この研究成果は、次のような分野への波及効果が期待されます。(1)気道疾患の治療法の開発: 気道上皮および間充織の分化プロセスの理解を深めることで、気道疾患の治療法の開発が可能となります。例えば、気道再生療法や気道再建手術などの治療法に直接応用できます。(2)幹細胞療法の発展: 組織幹細胞や間充織細胞を用いた幹細胞療法の開発に役立ちます。特に、気道再生や肺再生における幹細胞療法の進歩が期待されます。総合的に、本研究は気道および肺の生物学的理解に加えて、疾患治療や再生医療の進歩に向けた重要な基盤を提供することが期待されます。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (27 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (14 results) (of which Int'l Joint Research: 8 results,  Invited: 11 results) Remarks (4 results)

  • [Int'l Joint Research] シンシナティ小児科病院(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] シンシナティ小児科病院、オルガノイド医学研究センター(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] シンシナティ小児科病院(米国)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Directed differentiation of human pluripotent stem cells into diverse organ-specific mesenchyme of the digestive and respiratory systems2022

    • Author(s)
      Kishimoto K, Iwasawa K, Sorel A, Ferran-Heredia C, Han L, Morimoto M, Wells JM, Takebe T, Zorn AM.
    • Journal Title

      Nat Protoc

      Volume: 17 Issue: 11 Pages: 2699-2719

    • DOI

      10.1038/s41596-022-00733-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfβ-Id2 axis, for tissue regeneration2021

    • Author(s)
      Hirofumi Kiyokawa, Akira Yamaoka, Chisa Matsuoka, Tomoko Tokuhara, Takaya Abe, Mitsuru Morimoto
    • Journal Title

      Developmental Cell

      Volume: 56 Issue: 13 Pages: 1917-1929

    • DOI

      10.1016/j.devcel.2021.05.016

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular crosstalk in tracheal development and its recurrence in adult tissue regeneration2021

    • Author(s)
      Hirofumi Kiyokawa, Mitsuru Morimoto
    • Journal Title

      Developmental Dynamics

      Volume: 250 Issue: 11 Pages: 1552-1567

    • DOI

      10.1002/dvdy.345

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] 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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Scrap and Reconstruction of Lung Fibrosis using Alveolar Organoid2023

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      Keystone Symposia:
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identifying a lung stem cell subpopulation by combining single-cell morphometrics, organoid culture, and transcriptomics.2022

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      FASEB Science Research Conference; The Lung Epithelium Conference: In Health and Disease
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Lung development in mouse and human.2022

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      The Oxford Conference on Modelling and Control of Breathing.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Trachea Development and Reconstruction2021

    • Author(s)
      森本充
    • Organizer
      CLEAR Consortium Annual Symposium 2021 (米国 オンライン)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 気管細胞の起源の発見と、その分子的理解からヒト気管の再建への挑戦2021

    • Author(s)
      森本充
    • Organizer
      第61回日本呼吸器学会学術講演 シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Trachea Development and Reconstruction2021

    • Author(s)
      森本充
    • Organizer
      The Taiwanese Society of Developmental Biology 2021:International Conference of Developmental Biology, Stem Cells and Regenerative Medicine.(台湾 オンライン))
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 幹細胞研究からオルガノイド開発、そして肺疾患解析へ、2021

    • Author(s)
      森本充
    • Organizer
      第42回日本炎症・再生医学会 シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfβ-Id2 axis, for tissue regeneration.2021

    • Author(s)
      森本充
    • Organizer
      The 25th congress of the Asian Pacific Society of Respiology; Emerging Talent Symposia.
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfβ-Id2 axis, for tissue regeneration.2021

    • Author(s)
      森本充
    • Organizer
      FUSION conference; Epithelial Stem Cell - Niche Interactions in Lung.(イギリス オンライン)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 1細胞解像度で見る呼吸器細胞パターニング2020

    • Author(s)
      森本充
    • Organizer
      第5回日本肺高血圧・肺循環学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 1細胞解像度で見る呼吸器幹細胞の発生2020

    • Author(s)
      森本充
    • Organizer
      第60回日本呼吸器学会学術講演 シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 1細胞解像度で見る呼吸器幹細胞の発生2020

    • Author(s)
      森本充
    • Organizer
      第56回日本周産期・新生児医学会学術集会 教育講演
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Wnt signaling confers tracheal identity in mouse and human2020

    • Author(s)
      Mitsuru Morimoto
    • Organizer
      From Stem Cells to Human Development, the Company od Biologist.
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Wnt signaling confers tracheal identity in mouse and human2020

    • Author(s)
      森本充
    • Organizer
      Wnt研究会2021
    • Related Report
      2020 Annual Research Report
  • [Remarks] ES/iPS細胞からのヒト臓器の間充織細胞作製法 -正常な臓器形成の理解に基づく臓器細胞の作出-

    • URL

      https://www.riken.jp/press/2022/20220818_1/index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] プレスリリース マウス胎児の中に見つけた呼吸器再生のヒント

    • URL

      https://www.riken.jp/press/2021/20210615_1/index.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] 理化学研究所 呼吸器形成研究チーム

    • URL

      https://lungdev.riken.jp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 呼吸器の発生をつかさどるメカニズムの解明 -発生現象の発見に基づくES細胞から気管組織の作出へ-

    • URL

      https://www.riken.jp/press/2020/20200827_2/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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