Control of satellite cell function in muscle regeneration and its disruption in ageing

Skeletal muscle contains a designated population of adult stem cells, called satellite cells, which are generally quiescent. In homeostasis, satellite cells proliferate only sporadically and usually by asymmetric cell division to replace myofibres damaged by daily activity and maintain the stem cell pool. However, satellite cells can also be robustly activated upon tissue injury, after which they undergo symmetric divisions to generate new stem cells and numerous proliferating myoblasts that later differentiate to muscle cells (myocytes) to rebuild the muscle fibre, thereby supporting skeletal muscle regeneration. Recent discoveries show that satellite cells have a great degree of population heterogeneity, and that their cell fate choices during the regeneration process are dictated by both intrinsic and extrinsic mechanisms. Extrinsic cues come largely from communication with the numerous distinct stromal cell types in their niche, creating a dynamically interactive microenvironment. This Review discusses the role and regulation of satellite cells in skeletal muscle homeostasis and regeneration. In particular, we highlight the cell-intrinsic control of quiescence versus activation, the importance of satellite cell–niche communication, and deregulation of these mechanisms associated with ageing. The increasing understanding of how satellite cells are regulated will help to advance muscle regeneration and rejuvenation therapies. Satellite cells are skeletal muscle stem cells that are largely quiescent. They are activated upon muscle damage and differentiate into muscle cells or return to quiescence. These processes are controlled by cell-intrinsic mechanisms and by signals from the niche, and are deregulated in ageing, leading to impaired muscle regeneration.