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Abstract
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.