Epigenetic Regulation of Muscle Stem Cells During Skeletal Muscle Regeneration and Disease

Skeletal muscle possesses a remarkable capacity to regenerate upon injury thanks to the presence of a population of stem cells called muscle satellite cells (MuSCs). These cells, normally quiescent in resting conditions, become activated by extracellular cues released in the regenerative environment, expand and then differentiate into mature myofibers to properly repair injured muscles. During regenerative cycles, MuSCs undergo dramatic epigenetic changes that dictate activation or repression of specific transcriptional programs needed to transit along different cell fates. Epigenetic dynamics along MuSCs-mediated regeneration are therefore paradigmatic in regenerative medicine to understand how epigenetic factors influence stem cells’ fate decisions and repair capacity. In this chapter, we will first discuss the transcriptional hierarchies underlying the specification and activity of MuSCs. Moreover, we will report on the recent literature regarding the molecular mechanisms underlying the epigenetic changes that drive fate choices of MuSCs, highlighting in particular the role of chromatin-modifying enzymes and their functional cooperation with MuSCs-specific transcription factors. Finally, we will comment on the growing body of evidence showing how deregulated epigenetic regulation of such events leads to defects in the regenerative capacity of skeletal muscle during aging and in chronic degenerative diseases, such as muscular dystrophies.