Notch signaling in the regulation of skeletal muscle stem cells

Abstract

Resident muscle stem cells are satellite cells that are responsible for the postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In healthy adult muscle, satellite cells are mitotically quiescent, but are activated in response to stimulation such as muscle injury. Once activated, these cells then proliferate, with the majority of satellite cell progeny undergoing myogenic differentiation while the other cells return to a quiescent state and self-renew. Notch signaling is a highly conserved pathway that controls stem cell function in a variety of tissues including skeletal muscle. In this review, we discuss how Notch signaling acts as a regulator of the satellite cell pool and their fate decisions. Recent mouse genetic studies revealed that Notch signaling is essential for maintaining the satellite cell quiescent state in uninjured muscle, while it also allows for population expansion and promotes self-renewal when satellite cells are activated. Notably, diminished Notch activity in satellite cells is associated with muscle disorders such as age-related sarcopenia and muscular dystrophy. This review provides an overview of the multiple aspects of Notch signaling in muscle development and regeneration, and highlights recent studies that address its role in physiological and pathological conditions within muscle.

Keywords

• satellite cells
• skeletal muscle
• notch1
• notch2