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

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

Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. · pubmed

Paper

Abstract

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper claims that MRG15 is a critical epigenetic regulator that, when dysregulated, impairs muscle regeneration during aging. This research addresses the underlying mechanisms of muscle stem cell decline in aging, which is directly related to the biological processes of aging and potential interventions for age-related decline in muscle function.

Author of this paper? Send a correction.