Skeletal muscle satellite cells can spontaneously enter an alternative mesenchymal pathway.
We show that muscle satellite cells, traditionally considered as committed myogenic precursors, are comprised of Pax7-expressing progenitors that preserve a mesenchymal repertoire extending beyond a mere myogenic potential. Mouse satellite cells from freshly isolated single myofibers, cultured individually in serum-rich growth medium, produced myogenic and non-myogenic clones. Only the myogenic clones expressed muscle-specific transcription factors and formed myotubes. Pax7 was initially expressed in all clones, but subsequently was associated only with the myogenic clones. Some cells in the non-myogenic clones expressed alpha-smooth muscle actin and nestin whereas others differentiated into mature adipocytes. This type of cell composition mirrors characteristics of mesenchymal stem cell progeny. Overall, individual myofibers persistently gave rise to both clonal phenotypes, but the ratio of myogenic to non-myogenic clones randomly varied among fibers. This randomness indicates that clonal dichotomy reflects satellite cell suppleness rather than pre-fated cell heterogeneity. We conclude that satellite cells possess mesenchymal plasticity, being able to commit either to myogenesis or to a mesenchymal alternative differentiation (MAD) program.
Shefer
Gabi
G
Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Wleklinski-Lee
Monika
M
Yablonka-Reuveni
Zipora
Z
D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D002448:Cell Adhesion; D002454:Cell Differentiation; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D051763:PAX7 Transcription Factor; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D000199:Actins; D001391:Azo Compounds; D005456:Fluorescent Dyes; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D049452:Green Fluorescent Proteins; C011049:oil red O