Epigenetic control of adult skeletal muscle stem cell functions

Abstract

Skeletal muscle regeneration in the adult (de novo myogenesis) depends on a resident population of muscle stem cells (satellite cells) that are normally quiescent. In response to injury or stress, satellite cells are activated and expand as myoblast cells that differentiate and fuse to form new muscle fibers or return to quiescence to maintain the stem cell pool (self-renewal). Satellite cell-dependent myogenesis is a well-characterized multi-step process orchestrated by muscle-specific transcription factors, such as Pax3/Pax7 and members of the MyoD family of muscle regulatory factors, and epigenetically controlled by mechanisms such as DNA methylation, covalent modification of histones and non-coding RNAs. Recent results from next-generation genome-wide sequencing have increased our understanding about the highly intricate layers of epigenetic regulation involved in satellite cell maintenance, activation, differentiation and self-renewal, and their cross-talk with the muscle-specific transcriptional machinery.

Keywords: DNA methylation; chromatin modifications; epigenetic regulation; histone code; muscle stem cell; myogenesis; satellite cells; signal transduction; skeletal muscle; transcription factors.