Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G0) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating fac- tors. The resulting GAlert SCs are adapted to regener- ative cues and regenerate injured muscles more effi- ciently, but whether they provide any long-term benefits to SCs is unknown. Here, we report that em- bryonic myogenic progenitors lacking the phospha- tase and tensin homolog (Pten) exhibit enhanced proliferation and differentiation, resulting in muscle hypertrophy but fewer SCs in adult muscles. Interest- ingly, Pten null SCs are predominantly in the GAlert state, even in the absence of an injury. The GAlert SCs are deficient in self-renewal and subjected to accelerated depletion during regeneration and aging and fail to repair muscle injury in old mice. Our findings demonstrate a key requirement of Pten in G0 entry of SCs and provide functional evidence that prolonged GAlert leads to stem cell depletion and regenerative failure.
Date of this Version
Yue F, Bi P, Wang C, Li J, Liu X, Kuang S. Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells. Cell Rep. 2016 Nov 22;17(9):2340-2353. doi: 10.1016/j.celrep.2016.11.002.