In response to muscle injury, muscle stem cells integrate environmental cues in the damaged tissue to mediate regeneration. These environmental cues are tightly regulated to ensure expansion of muscle stem cell population to repair the damaged myofibers while allowing repopulation of the stem cell niche. These changes in muscle stem cell fate result from changes in gene expression that occur in response to cell signaling from the muscle environment. Integration of signals from the muscle environment leads to changes in gene expression through epigenetic mechanisms. Such mechanisms, including post-translational modification of chromatin and nucleosome repositioning, act to make specific gene loci more, or less, accessible to the transcriptional machinery. In youth, the muscle environment is ideally structured to allow for coordinated signaling that mediates efficient regeneration. Both age and disease alter the muscle environment such that the signaling pathways that shape the healthy muscle stem cell epigenome are altered. Altered epigenome reduces the efficiency of cell fate transitions required for muscle repair and contributes to muscle pathology. However, the reversible nature of epigenetic changes holds out potential for restoring cell fate potential to improve muscle repair in myopathies. In this review, we will describe the current knowledge of the mechanisms allowing muscle stem cell fate transitions during regeneration and how it is altered in muscle disease. In addition, we provide some examples of how epigenetics could be harnessed therapeutically to improve regeneration in various muscle pathologies.

中文翻译：

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骨骼肌再生过程中卫星细胞命运的表观遗传调控

作为对肌肉损伤的反应，肌肉干细胞将环境信号整合到受损组织中以介导再生。这些环境线索受到严格调控，以确保肌肉干细胞群的扩张以修复受损的肌纤维，同时允许干细胞生态位的重新增殖。肌肉干细胞命运的这些变化是由于响应肌肉环境的细胞信号而发生的基因表达变化。来自肌肉环境的信号的整合通过表观遗传机制导致基因表达的变化。这些机制，包括染色质的翻译后修饰和核小体重新定位，可以使特定的基因位点或多或少地接近转录机制。在青年时期，肌肉环境的理想结构是允许协调的信号传导，从而介导有效的再生。年龄和疾病都会改变肌肉环境，从而改变塑造健康肌肉干细胞表观基因组的信号通路。改变的表观基因组降低了肌肉修复所需的细胞命运转变的效率，并导致肌肉病理。然而，表观遗传变化的可逆性质提供了恢复细胞命运潜力以改善肌病中肌肉修复的潜力。在这篇综述中，我们将描述目前关于在再生过程中允许肌肉干细胞命运转变的机制以及它在肌肉疾病中如何改变的知识。此外，