Orienting Muscle Stem Cells for Regeneration in Homeostasis, Aging, and Disease

Muscle stem cells, or satellite cells, are required for skeletal muscle maintenance, growth, and repair. Following satellite cell activation, several factors drive asymmetric cell division to generate a stem cell and a proliferative progenitor that forms new muscle. The balance between symmetric self-renewal and asymmetric division significantly impacts the efficiency of regeneration. In this Review, we discuss the relationship of satellite cell heterogeneity and the establishment of polarity to asymmetric division, as well as how these processes are impacted in homeostasis, aging, and disease. We also highlight therapeutic opportunities for targeting satellite cell polarity and self-renewal to stimulate muscle regeneration. In this Review, Feige et al. discuss the relationship of muscle stem/satellite cell heterogeneity and the establishment of polarity to asymmetric division, as well as how these processes are impacted in homeostasis, aging, and disease. They also highlight therapeutic opportunities for targeting satellite cell polarity and self-renewal to stimulate muscle regeneration.