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.
Kuang
Shihuan
S
The Sprott Center for Stem Cell Research, Ottawa Health Research Institute, Molecular Medicine Program, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Kuroda
Kazuki
K
Le Grand
Fabien
F
Rudnicki
Michael A
MA
D000818:Animals; D002454:Cell Differentiation; D002469:Cell Separation; D017690:Cell Transplantation; D005260:Female; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism
D008164:Luminescent Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D051880:Receptors, Notch