Asymmetric Self-Renewal and Commitment of Satellite Stem Cells in Muscle

Satellite cells play a central role in mediating the growth and regeneration of skeletal muscle. However, whether satellite cells are stem cells, committed progenitors, or dedifferentiated myoblasts has remained unclear. Using Myf5-Cre and ROSA26-YFP Cre-reporter alleles, we observed that in vivo 10% of sublaminar Pax7-expressing satellite cells have never expressed Myf5. Moreover, we found that Pax7+/Myf5− satellite cells gave rise to Pax7+/Myf5+ satellite cells through apical-basal oriented divisions that asymmetrically generated a basal Pax7+/Myf5− and an apical Pax7+/Myf5+ cells. Prospective isolation and transplantation into muscle revealed that whereas Pax7+/Myf5+ cells exhibited precocious differentiation, Pax7+/Myf5− cells extensively contributed to the satellite cell reservoir throughout the injected muscle. Therefore, we conclude that satellite cells are a heterogeneous population composed of stem cells and committed progenitors. These results provide critical insights into satellite cell biology and open new avenues for therapeutic treatment of neuromuscular diseases.