SOX7 Is Required for Muscle Satellite Cell Development and Maintenance

Satellite cells are skeletal-muscle-specific stem cells that are activated by injury to proliferate, differentiate, and fuse to enable repair. SOX7, a member of the SRY-related HMG-box family of transcription factors is expressed in quiescent satellite cells. To elucidate SOX7 function in skeletal muscle, we knocked down Sox7 expression in embryonic stem cells and primary myoblasts and generated a conditional knockout mouse in which Sox7 is excised in PAX3+ cells. Loss of Sox7 in embryonic stem cells reduced Pax3 and Pax7 expression. In vivo, conditional knockdown of Sox7 reduced the satellite cell population from birth, reduced myofiber caliber, and impaired regeneration after acute injury. Although Sox7-deficient primary myoblasts differentiated normally, impaired myoblast fusion and increased sensitivity to apoptosis in culture and in vivo were observed. Taken together, these results indicate that SOX7 is dispensable for myogenesis but is necessary to promote satellite cell development and survival. •Loss of Sox7 in embryonic stem cells impairs myogenic precursor production•SOX7 regulates Pax7 expression•SOX7 protects satellite cells from apoptosis after injury•Loss of Sox7 in satellite cells impairs myoblast fusion and muscle regeneration In this article, Wiper-Bergeron and colleagues demonstrate that the transcription factor SOX7 is required for skeletal muscle satellite cell development and maintenance. SOX7 regulates Pax7 expression, and loss of SOX7 leads to fewer satellite cells that are more sensitive to apoptosis. Furthermore, loss of Sox7 in satellite cells results in smaller myotubes and impaired regeneration after injury in post-natal muscle.