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

Cell. 2007 Jun 1;129(5):999-1010. doi: 10.1016/j.cell.2007.03.044.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Separation
  • Cell Transplantation
  • Female
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / metabolism
  • Myogenic Regulatory Factor 5 / metabolism
  • PAX7 Transcription Factor / metabolism
  • Receptors, Notch / metabolism
  • Satellite Cells, Skeletal Muscle / cytology*
  • Satellite Cells, Skeletal Muscle / metabolism

Substances

  • Luminescent Proteins
  • Myf5 protein, mouse
  • Myogenic Regulatory Factor 5
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Receptors, Notch