Muscle Stem Cell Quiescence: Controlling Stemness by Staying Asleep

Muscle stem cells (MuSCs) are tissue-resident stem cells required for growth and repair of skeletal muscle, that are otherwise maintained in a cell-cycle-arrested state called quiescence. While quiescence was originally believed to be a state of cellular inactivity, increasing evidence suggests that quiescence is dynamically regulated and contributes to stemness, the long-term capacity to maintain regenerative functions. Here, we review the current understanding of MuSC quiescence and highlight recently discovered molecular markers, which differentiate depth of quiescence and influence self-renewal capacity. We also discuss how quiescent MuSCs integrate paracrine factors from their niche and dynamically regulate cell signaling, metabolism and proteostasis as they anticipate physiological needs, and how perturbing these cues during aging impairs muscle regeneration.

Automated summary

MuSCs are tissue-resident stem cells crucial for skeletal muscle growth and repair. Quiescence, previously thought of as cellular inactivity, is now understood to be dynamically regulated and important for maintaining stemness. Molecular markers differentiating quiescence depth and influencing self-renewal capacity have been discovered, along with the role of paracrine factors in regulating cell signaling, metabolism, and proteostasis in MuSCs. Disrupting these cues during aging can impair muscle regeneration.