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<p>Skeletal muscle aging is characterized by a functional decline in muscle stem cells (MuSCs), yet the key regulatory mechanisms driving this deterioration remain poorly understood. By integrating transcriptomic profiles from aged MuSCs with data from C2C12 cells exposed to spaceflight conditions (which mimic an aging-like phenotype), we identified MORF4-related gene on chromosome 15 (MRG15) as a putative epigenetic regulator involved in age-related myogenic decline. Using a MuSC-specific inducible knockout (iKO) mouse model, we found that loss of MRG15 severely compromises myogenic differentiation and muscle regeneration. Subsequent RNA sequencing of iKO MuSCs, combined with ChIP-seq analysis of histone modifications, revealed that MRG15 modulates the chromatin landscape of myogenic genes through interaction with MyoD, thereby facilitating transcriptional activation and differentiation. Our findings establish MRG15 as a critical epigenetic regulator that cooperates with MyoD to orchestrate chromatin remodeling, thereby promoting transcriptional activation of the myogenic program. Dysregulation of MRG15 may underlie impaired muscle regeneration during aging.</p>

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MRG15 decline in aged/injured MuSCs hinders regeneration via differentiation defects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月25日

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  • Zhuoyang Li,
  • Mei Ma,
  • Siyi Shen,
  • Ruisen Ma,
  • Wenqing Kong,
  • Yuting Wu,
  • Qiurong Ding,
  • Hao Ying,
  • Yuying Li

摘要

Skeletal muscle aging is characterized by a functional decline in muscle stem cells (MuSCs), yet the key regulatory mechanisms driving this deterioration remain poorly understood. By integrating transcriptomic profiles from aged MuSCs with data from C2C12 cells exposed to spaceflight conditions (which mimic an aging-like phenotype), we identified MORF4-related gene on chromosome 15 (MRG15) as a putative epigenetic regulator involved in age-related myogenic decline. Using a MuSC-specific inducible knockout (iKO) mouse model, we found that loss of MRG15 severely compromises myogenic differentiation and muscle regeneration. Subsequent RNA sequencing of iKO MuSCs, combined with ChIP-seq analysis of histone modifications, revealed that MRG15 modulates the chromatin landscape of myogenic genes through interaction with MyoD, thereby facilitating transcriptional activation and differentiation. Our findings establish MRG15 as a critical epigenetic regulator that cooperates with MyoD to orchestrate chromatin remodeling, thereby promoting transcriptional activation of the myogenic program. Dysregulation of MRG15 may underlie impaired muscle regeneration during aging.