GSE135837
Estrogen receptor ß regulates skeletal muscle mass and muscle stem cell proliferation in young female mice
The female sex hormone estrogens plays a critical role in maintaining muscle mass and muscle stem cell (MuSCs) functions. However, it is still unclear about downstream pathways of estrogens including its receptors that are expressed in both skeletal muscle tissue and MuSCs. To study the specific role of estrogen receptor ß (ERß), one of two main types of estrogen receptors, in skeletal muscle and MuSCs, we generated muscle-specific ERß-knockout (mKO) mice and muscle stem cell-specific ERß-knockout (scKO) mice. Here, we show that muscle-specific ERß-deficient induced decreased muscle strength and fast-type muscle mass in young female mice. Furthermore, muscle stem cell-specific ERß-deficient young female mice but not male exhibited impaired muscle regeneration ability after acute muscle injury, accompanied by a decreased proliferation rate of muscle stem cells. RNA sequencing analysis showed that the loss of ERß in muscle stem cells changes the expression of cell cycle associated genes and niche component factors including laminin and collagen. Thus, our characterization of mKO and scKO mice indicate that the estrogen-ERß pathway is a sex-specific regulatory mechanism that controls both skeletal muscle mass and the proliferation of muscle stem cell in females and could be of importance in a therapeutic context. Overall design: mRNA profiles of primary satellite cells obtained from Control and ERß cKO mice were generated by deep sequencing, in triplicate, using Illumina Miseq.