Elucidation of Muscle Stem Cell Heterogeneity and Development of Regenerative Therapies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17679
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: University 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
• 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

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.

Free Research Field

骨格筋生物学

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。