Global analysis of functional maintenance mechanisms in muscle satellite cells.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Hayashi Shinichiro 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 室長 (10732381)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨格筋 / 筋衛星細胞 / Pax7 / single核RNA-seq

Outline of Final Research Achievements

Pax7, a critical transcription factor in muscle stem cells, plays a vital role, though its cofactors, target genes, and regulatory mechanisms are poorly understood. To address this gap, we employed Pax7-HA knock-in mice (Pax7-HA KI) to study its transcriptional regulatory network specifically within muscle stem cells. Our goal was to uncover the mechanisms governing their function and long-term maintenance. Using FACS, we isolated satellite cells from Pax7-HA KI and faced challenges in identifying Pax7 target genes via ChIP-seq due to limited DNA yield. As an alternative, single-nucleus RNA-seq was used to profile gene expression in Pax7-high expressing satellite cells. UMAP analysis identified distinct cell populations and revealed crucial genes for their functionality.
This study provides insights into transcriptional regulation in muscle stem cells, highlighting potential therapeutic targets to enhance their regenerative capacity in muscular dystrophy and related disorders.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、筋衛星細胞で高発現する遺伝子およびタンパク質が明らかとなった。今後、本研究で得られた因子についての解析を継続することにより、筋衛星細胞の未分化性維持機構が解明され、筋ジストロフィーの治療法へと応用されることが期待される。