Epigenetic regulation of satellite cell activation during muscle regeneration

Skeletal muscle regeneration is mediated by myogenic cell populations that reside in the muscle and behave as adult stem cells [1-3]. In the present article we will focus on satellite cells, which represent the best characterized population of adult muscle stem cells. Satellite cells are a population of mononuclear cells that reside between the muscle fiber and the basal lamina [1,4].While satellite cells spend most of their lifetime in a quiescent state, upon muscle damage they can re-enter the cell cycle and either: undergo a symmetric cell division to self-renew and expand the satellite cell population; or undergo an asymmetric cell division that results in the cell on the basal lamina side maintaining the satellite cell identity, while the cell adjacent to the muscle fiber enters the myogenic differentiation program [5,6]. Cell fate decisions undertaken by the satellite cells upon muscle damage are thought to be regulated through epigenetic mechanisms that modify the structure of chromatin without changing the DNA sequence. These epigenetic changes lead to altered gene expression profiles that contribute to defining cellular identity. Understanding the nature, origin and raison d'être of these epigenetic modifications in the regenerating muscle will be critical to determining how satellite cells can be maintained ex vivo such that this adult stem cell population can be amplified for therapeutic use to treat muscle-wasting diseases.Genetic screens for mutations that caused patterning defects in Drosophila led to the identification of Polycomb group (PcG) proteins, which act to repress developmentally regulated gene expression [7,8]. Further screening to identify genes that rescued the Polycomb phenotype resulted in the identification of an antagonistic group of proteins, termed Trithorax group (TrxG) proteins, which act to establish high levels of transcription from these same developmentally regulated loci. Over the past 5 years, studies in human and mouse embry