[HTML][HTML] Asymmetric self-renewal and commitment of satellite stem cells in muscle

S Kuang, K Kuroda, F Le Grand, MA Rudnicki - Cell, 2007 - cell.com
Cell, 2007cell.com
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 …
Summary
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.
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