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

Zhuoyang Li1, Mei Ma1, Siyi Shen1

  • 1Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Cell Regeneration (London, England)
|January 24, 2026
PubMed

Insights

Aging muscle stem cells (MuSCs) decline functionally. We found MORF4-related gene on chromosome 15 (MRG15) is crucial for muscle regeneration and differentiation by regulating gene expression during aging.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Aging Research

Background:

  • Skeletal muscle aging involves functional decline in muscle stem cells (MuSCs).
  • The precise regulatory mechanisms behind this age-related deterioration are not fully understood.
  • Spaceflight conditions can mimic aging phenotypes in muscle cells.

Purpose of the Study:

  • To identify key epigenetic regulators involved in age-related myogenic decline.
  • To investigate the role of MORF4-related gene on chromosome 15 (MRG15) in muscle stem cell function and regeneration.
  • To elucidate the molecular mechanisms by which MRG15 influences the myogenic program.

Main Methods:

  • Integrated transcriptomic profiles from aged MuSCs and spaceflight-conditioned C2C12 cells.
  • Utilized a muscle stem cell-specific inducible knockout (iKO) mouse model for MRG15.
  • Performed RNA sequencing and ChIP-seq analysis of histone modifications in iKO MuSCs.

Main Results:

  • Loss of MRG15 in MuSCs significantly impairs myogenic differentiation and muscle regeneration.
  • MRG15 interacts with MyoD to modulate the chromatin landscape of myogenic genes.
  • MRG15 facilitates the transcriptional activation of the myogenic program through chromatin remodeling.

Conclusions:

  • MRG15 is a critical epigenetic regulator essential for muscle regeneration and differentiation.
  • MRG15 cooperates with MyoD to orchestrate chromatin remodeling and activate the myogenic program.
  • Dysregulation of MRG15 may contribute to impaired muscle regeneration observed during aging.
Keywords:
AgingDifferentiationMRG15Muscle stem cellSkeletal muscle regeneration

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