Muscle stem cells and reversible quiescence: The role of sprouty

Quiescence is a critical determinant for sustained stem cell function throughout life. Disruption of cellular quiescence leads to loss of the stem cell pool and impaired tissue repair. In adult skeletal muscle, Pax7⁺ satellite cells (the muscle stem cells) are capable of self-renewal and differentiation in their endogenous environment during repair. In response to muscle injury, Pax7⁺ satellite cells enter the cell cycle; subpopulation returns to quiescence to fully replenish the satellite cell pool while others contribute to myofiber repair. We demonstrate that Sprouty1 (Spry1), an inhibitor of receptor tyrosine kinase signaling is required for the return to quiescence of the self-renewing Pax7⁺ satellite cell pool during repair. The temporal regulation of Spry1 expression during repair and its functional requirement in a subpopulation of cycling Pax7⁺ cells during repair ensure that tissue regeneration and re-establishment of the dormant stem cell pool are coordinated.