Nat Cell Biol. 2016 Sep;18(9):930-40. doi: 10.1038/ncb3401. Epub 2016 Aug 22.

Sex hormones establish a reserve pool of adult muscle stem cells.

Kim JH¹, Han GC¹, Seo JY¹, Park I¹, Park W¹, Jeong HW¹, Lee SH², Bae SH¹, Seong J¹, Yum MK¹, Hann SH¹, Kwon YG³, Seo D^1,4, Choi MH², Kong YY¹.

Abstract

Quiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells 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 myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration.