Reduced differentiation potential of primary MyoD-/- myogenic cells derived from adult skeletal muscle

Luc A. Sabourin, Adele Girgis-Gabardo, Patrick Scale, Atsushi Asakura, Michael A. Rudnicki

Research output: Contribution to journalArticlepeer-review

245 Scopus citations

Abstract

To gain insight into the regeneration deficit of MyoD-/- muscle, we investigated the growth and differentiation of cultured MyoD-/- myogenic cells. Primary MyoD-/- myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c- met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD- /- myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD-/- myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD-/- cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD-/- myogenic cells. Mixing of lacZ- labeled MyoD-/- cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD-/- myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell.

Original languageEnglish (US)
Pages (from-to)631-643
Number of pages13
JournalJournal of Cell Biology
Volume144
Issue number4
DOIs
StatePublished - Feb 22 1999

Keywords

  • Differentiation
  • MyoD
  • Myogenic regulatory factor
  • Proliferation
  • Satellite cell

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