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Elucidation of the Skeletal Muscle Microenvironment to Improve Transplantation Efficiency of Muscle Stem Cells

Research Project

Project/Area Number 20K23283
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0909:Sports sciences, physical education, health sciences, and related fields
Research InstitutionUniversity of Tsukuba

Principal Investigator

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

Project Period (FY) 2020-09-11 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords骨格筋幹細胞 / 骨格筋 / 細胞移植 / 幹細胞ニッシェ / 遺伝性筋疾患 / サルコペニア / 筋ジストロフィー / 筋再生 / シングルセル解析 / 幹細胞移植 / 微小環境 / 放射線
Outline of Research at the Start

骨格筋の可塑性を制御する骨格筋幹細胞は生体内で唯一骨格筋線維を再生できる幹細胞であることから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。しかし移植効率の低さから治療効果は現在までのところ得られていない。本研究は幹細胞移植をされるレシピエント側の移植環境に着目し、どのような移植環境が幹細胞の生着に重要かを細胞・分子レベルで解き明かすことを目的とする。本研究成果は筋疾患等への細胞治療に向けて、新たなアプローチを提供する。

Outline of Final Research Achievements

This research focused on improving the transplantation efficiency of skeletal muscle stem cells by examining their microenvironment, niche. Skeletal muscle stem cells are crucial for muscle regeneration and are expected to be used in treating sarcopenia (age-related muscle loss) and muscular dystrophy. However, the low efficiency of transplantation has been a challenge. In this study, we identified GPR116 as a key factor for maintaining skeletal muscle stem cells. It was found that the absence of GPR116 leads to a decrease in the number of stem cells and reduces their ability to maintain a quiescent state. These findings contribute to the development of new treatments and are expected to aid in the future treatment of muscle disease

Academic Significance and Societal Importance of the Research Achievements

本研究では、骨格筋幹細胞の移植効率向上を目指し、骨格筋幹細胞の微小環境(ニッシェ)に注目しました。骨格筋幹細胞は筋肉の再生に重要で、加齢による筋力低下(サルコペニア)や遺伝性筋疾患(筋ジストロフィー)の治療に役立つと期待されています。研究の結果、GPR116という因子が骨格筋幹細胞の維持に重要であることを発見しました。骨格筋幹細胞のGPR116が欠けると、微小環境との相互作用が低下し、その結果幹細胞の数が減少し、休眠状態を保つ力が弱まります。この分子の発見により、骨格筋幹細胞のGPR116の発現を保つための微小環境を整えることで、より効果的な幹細胞移植を目指せると考えます。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (19 results)

All 2023 2022 2021 2020 Other

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Remarks (1 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] Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction2023

    • Author(s)
      Tani Hidenori、Sadahiro Taketaro、Yamada Yu、Isomi Mari、Yamakawa Hiroyuki、Fujita Ryo、Abe Yuto、Akiyama Tatsuya、Nakano Koji、Kuze Yuta、Seki Masahide、Suzuki Yutaka、Fujisawa Manabu、Sakata-Yanagimoto Mamiko、Chiba Shigeru、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Circulation

      Volume: 147 Issue: 3 Pages: 223-238

    • DOI

      10.1161/circulationaha.121.058655

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High Throughput Screening of Mitochondrial Bioenergetics in Myoblasts and Differentiated Myotubes2023

    • Author(s)
      Takeda Kohei、Takemasa Tohru、Fujita Ryo
    • Journal Title

      Methods in Molecular Biology

      Volume: 2640 Pages: 89-98

    • DOI

      10.1007/978-1-0716-3036-5_7

    • ISBN
      9781071630358, 9781071630365
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool2022

    • Author(s)
      Senechal Charlotte、Fujita Ryo、Jamet Solene、Maiga Arhamatoulaye、Dort Junio、Orfi Zakaria、Dumont Nicolas A.、Bouvier Michel、Crist Colin
    • Journal Title

      Cell Reports

      Volume: 41 Issue: 7 Pages: 111645-111645

    • DOI

      10.1016/j.celrep.2022.111645

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct Reprogramming as a Novel Approach for Cardiovascular Regeneration2021

    • Author(s)
      Fujita Ryo、Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      Pediatric Cardiology and Cardiac Surgery

      Volume: 37 Issue: 1 Pages: 10-17

    • DOI

      10.9794/jspccs.37.10

    • NAID

      130008117314

    • ISSN
      0911-1794, 2187-2988
    • Year and Date
      2021-04-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nuclear factor E2-related factor 2 (NRF2) deficiency accelerates fast fibre type transition in soleus muscle during space flight2021

    • Author(s)
      Hayashi Takuto, Kudo Takashi, Fujita Ryo, Fujita Shin-ichiro, Tsubouchi Hirona, Fuseya Sayaka, Suzuki Riku, Hamada Michito, Okada Risa, Muratani Masafumi, Shiba Dai, Suzuki Takafumi, Warabi Eiji, Yamamoto Masayuki, Takahashi Satoru
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 787-787

    • DOI

      10.1038/s42003-021-02334-4

    • NAID

      120007185357

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Yamakawa Hiroyuki、Fujita Ryo、Yamada Yu、Abe Yuto、Murakata Yoshiko、Akiyama Tatsuya、Shu Tsugumine、Mizukami Hiroaki、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Circulation

      Volume: 143 Issue: 21 Pages: 2123-2125

    • DOI

      10.1161/circulationaha.120.052799

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Fujita Ryo、Abe Yuto、Yamada Yu、Akiyama Tatsuya、Mizukami Hiroaki、Shu Tsugumine、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 560 Pages: 87-92

    • DOI

      10.1016/j.bbrc.2021.04.121

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Satellite cell expansion is mediated by P-eIF2α dependent Tacc3 translation2021

    • Author(s)
      Fujita Ryo、Jamet Solene、Lean Graham、Cheng Harry Chun Man、Hebert Steven、Kleinman Claudia L.、Crist Colin
    • Journal Title

      Development

      Volume: 148

    • DOI

      10.1242/dev.194480

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] 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] 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] 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] 骨格筋幹細胞と微小環境をつなぐ接着型Gタンパク質共役型受容体の役割2022

    • Author(s)
      藤田諒
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 接着型Gタンパク質共役型受容体による骨格筋幹細胞維持メカニズム2022

    • Author(s)
      藤田諒
    • Organizer
      第8回 Matricell フォーラム
    • Related Report
      2022 Research-status Report
  • [Presentation] サルコペニア・筋疾患治療へ向けた骨格筋幹細胞の可能性2021

    • Author(s)
      藤田諒
    • Organizer
      BioJapan2021
    • Related Report
      2021 Research-status Report
  • [Presentation] Gタンパク質共役型受容体における骨格筋幹細胞の幹細胞性維持機構2021

    • Author(s)
      藤田諒
    • Organizer
      第76回日本体力医学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 骨格筋幹細胞の機能とサルコペニア2020

    • Author(s)
      藤田諒
    • Organizer
      第7回日本サルコペニア・フレイル学会大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] 筋肉の幹細胞が眠る仕組みを解明-筋疾患治療法の開発に貢献-

    • URL

      https://www.tsukuba.ac.jp/journal/medicine-health/20221117140000.html

    • Related Report
      2022 Research-status Report

URL: 

Published: 2020-09-29   Modified: 2025-01-30  

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