Sex hormones establish a reserve pool of adult muscle stem cells at puberty

Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty. Microarray analysis of Veh or DHT-injected 10-day-old mice s.c. injected with Veh or DHT. TA muscles were isolated 24 h after the injection.