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Elucidation of Muscle Stem Cell Heterogeneity and Development of Regenerative Therapies

Research Project

Project/Area Number 21K17679
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionUniversity of Tsukuba

Principal Investigator

Fujita Ryo  筑波大学, 医学医療系, 助教 (60770435)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords骨格筋幹細胞 / 幹細胞不均質性 / 筋再生 / 筋ジストロフィー / MyoDノックインマウス / サルコペニア / 骨格筋 / 幹細胞不均一性 / Dusp13 / Dusp27 / 遺伝性筋疾患 / 遺伝子組換えマウス / ヘテロジェネイティ
Outline of Research at the Start

生体内で唯一骨格筋線維を再生できる骨格筋幹細胞はサルコペニアや筋ジストロフィーなどの筋疾患への細胞治療が高く期待されている。骨格筋幹細胞は人間社会と同じように非常にヘテロな細胞の集まりであり、一つ一つの細胞に特性があると考えられている。しかし、それぞれの細胞同士がどのように相互作用しながら、我々の生体内で適切な筋再生・形成を担っているのかは明らかとなっていない。本研究では骨格筋幹細胞集団のそれぞれの細胞の持つ特性や細胞同士の相互作用を明らかにすることで、より効率的な筋再生治療の開発を目指す。

Outline of Final Research Achievements

Muscle stem cells (MuSCs) are the only stem cells in the body capable of regenerating muscle fibers, making them highly promising for regenerative treatments of muscle diseases such as sarcopenia and muscular dystrophy. This research aimed to identify key molecules essential for maintaining the stem cell properties of MuSCs, focusing on cell heterogeneity. We aimed to establish methods to maintain MuSCs with high regenerative potential (proliferation and differentiation) in a state closer to their in vivo condition. During the research period, we successfully created MyoD knock-in mice that visualize the heterogeneity of MuSCs, enabling us to distinguish between undifferentiated and activated cell populations. Additionally, from the analysis of these mice, we discovered molecules that are activated in specific cell populations and are responsible for the heterogeneity of MuSCs.

Academic Significance and Societal Importance of the Research Achievements

本研究は、骨格筋幹細胞の多様性とその分子基盤を解明することを目的とした。骨格筋幹細胞は、骨格筋の再生に不可欠な細胞であり、その幹細胞性を維持しつつ効率的に増殖させることが求められている。本研究では、遺伝子改変マウス(MyoDノックインマウス)を作成し、骨格筋幹細胞の未分化集団と活性化集団の違いを解析する手法を開発した。この研究開発により、特定の遺伝子が幹細胞の未分化維持や活性化に関与していることが明らかになり、本研究成果は加齢や遺伝性疾患による筋肉の減少(サルコペニアや筋ジストロフィー)に対する新しい治療法の開発に繋がる可能性がある。

Report

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

    (17 results)

All 2023 2022 2021 Other

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Generation of a MyoD knock-in reporter mouse line to study muscle stem cell dynamics and heterogeneity2023

    • Author(s)
      Fujita Ryo、Mizuno Seiya、Sadahiro Taketaro、Hayashi Takuto、Sugasawa Takehito、Sugiyama Fumihiro、Ono Yusuke、Takahashi Satoru、Ieda Masaki
    • Journal Title

      iScience

      Volume: 26 Issue: 5 Pages: 106592-106592

    • DOI

      10.1016/j.isci.2023.106592

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination2023

    • Author(s)
      Sadaki Shunya、Fujita Ryo、Hayashi Takuto、Nakamura Ayano、Okamura Yui、Fuseya Sayaka、Hamada Michito、Warabi Eiji、Kuno Akihiro、Ishii Akiko、Muratani Masafumi、Okada Risa、Shiba Dai、Kudo Takashi、Takeda Shin’ichi、Takahashi Satoru
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 4 Pages: 112289-112289

    • DOI

      10.1016/j.celrep.2023.112289

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The mitochondrial protein OPA1 regulates the quiescent state of adult muscle stem cells2022

    • Author(s)
      Baker Nicole、Wade Steven、Triolo Matthew、Girgis John、Chwastek Damian、Larrigan Sarah、Feige Peter、Fujita Ryo、Crist Colin、Rudnicki Michael A.、Burelle Yan、Khacho Mireille
    • Journal Title

      Cell Stem Cell

      Volume: 29 Issue: 9 Pages: 1315-1332.e9

    • DOI

      10.1016/j.stem.2022.07.010

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of muscle stem cells in sarcopenia2021

    • Author(s)
      Fujita Ryo
    • Journal Title

      Sarcopenia: Molecular Mechanism and Treatment Strategies

      Volume: - Pages: 109-138

    • DOI

      10.1016/b978-0-12-822146-4.00009-0

    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] サルコペニア克服に向けた骨格筋線維タイプ制御機構の解明2023

    • Author(s)
      藤田 諒; 定木 駿弥; 林 卓杜; 辻 諒介; 工藤 崇; 高橋 智
    • Organizer
      第10回 日本サルコペニア・フレイル学会大会/
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] MyoD ノックインマウスによる骨格筋幹細胞の運命制御機構の解明2023

    • Author(s)
      藤田諒
    • Organizer
      第9回日本筋学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] これであなたもネズミのように走れる!? 肉質制御機構の解明2023

    • Author(s)
      藤田諒
    • Organizer
      The 153rd Scienc-ome
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination2023

    • Author(s)
      Fujita Ryo; Sadaki Shunya; Takahashi Satoru
    • Organizer
      1st Symposium on "Skeletal muscle cells in Growth and Disease"
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 速筋線維の形成に不可欠な新規制御因子である大Maf転写因子の機能解析2022

    • Author(s)
      定木駿弥; 藤田 諒; 林 卓杜; 中村 綾乃; 岡村 結; 布施谷 清香; 濱田 理人; 蕨 栄治; 久野 朗広; 村谷匡史; 岡田 理沙;芝 大; 工藤 崇;高橋 智
    • Organizer
      日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Lunar Gravity Prevents Skeletal Muscle Atrophy, But Not Muscle Fiber Type Transition2022

    • Author(s)
      HAYASHI, Takuto;Fujita, Ryo;Okada, Risa;Hamada, Michito;Suzuki, Riku;Fuseya, Sayaka;Leckey, James;Kanai, Maho;Inoue, Yuri;Sadaki, Shunya;Nakamura, Ayano;Okamura, Yui;Abe, Chikara;Morita, Hironobu;Muratani, Masafumi;Kudo, Takashi;Shiba, Dai;Takahashi, Satoru
    • Organizer
      15th Annual Wernher von Braun Memorial Symposium
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大Maf転写因子は速筋線維を制御する主要な因子である2022

    • Author(s)
      定木駿弥;藤田, 諒;林卓杜;中村綾乃;岡村結;布施谷清香;濱田理人;蕨栄治;久野朗広;村谷匡史;岡田理沙;芝大;工藤崇;高橋, 智
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新規遺伝子改変マウスによる骨格筋幹細胞の運命制御機構の解明2021

    • Author(s)
      藤田諒、水野聖哉、貞廣威太郎、杉山文博、高橋智、家田真樹
    • Organizer
      第7回日本筋学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 宇宙環境を用いた骨格筋重力応答の解析2021

    • Author(s)
      高橋智、工藤崇、林卓杜、藤田諒
    • Organizer
      第7回日本筋学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Direct In Vivo Reprogramming of Fibroblasts into Cardiomyocytes as a Therapeutic Strategy for Heart Failure2021

    • Author(s)
      Taketaro Sadahiro, Yu Yamada, Fujita Ryo, Yuto Abe, Tatsuya Akiyama, Masaki Ieda
    • Organizer
      ISSCR/JSRM 2021 Tokyo International Symposium
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Book] 医学のあゆみ(骨格筋幹細胞の幹細胞性維持機構-休止期維持メカニズムを中心に-)2023

    • Author(s)
      藤田諒
    • Total Pages
      2
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2023 Annual Research Report
  • [Remarks] 第9回日本筋学会学術集会 Young Investigator's Award 最優秀賞

    • URL

      https://www.md.tsukuba.ac.jp/tmrc/news/20230824/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 筋肉を速筋タイプにする転写因子を同定 - 加齢や病気で低下した筋機能の改善方法開発に期待-

    • URL

      https://www.tsukuba.ac.jp/journal/medicine-health/20230324143000.html

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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