Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of α7 integrin-expressing myoblasts

Conrad L. Epting, Javier E Lopez, Anissa Pedersen, Courtney Brown, Paul Spitz, Philip C. Ursell, Harold S. Bernstein

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Skeletal muscle repair occurs through a programmed series of events including myogenic precursor activation, myoblast proliferation, and differentiation into new myofibers. We previously identified a role for Stem cell antigen-1 (Sca-1) in myoblast proliferation and differentiation in vitro. We demonstrated that blocking Sca-1 expression resulted in sustained myoblast cell division. Others have since demonstrated that Sca-1-null myoblasts display a similar phenotype when cultured ex vivo. To test the importance of Sca-1 during myogenesis in vivo, we employed a myonecrotic injury model in Sca-1-/- and Sca-1+/+ mice. Our results demonstrate that Sca-1-/- myoblasts exhibit a hyperproliferative response consisting of prolonged and accelerated cell division in response to injury. This leads to delayed myogenic differentiation and muscle repair. These data provide the first in vivo evidence for Sca-1 as a regulator of myoblast proliferation during muscle regeneration. These studies also suggest that the balance between myogenic precursor proliferation and differentiation is critical to normal muscle repair.

Original languageEnglish (US)
Pages (from-to)1125-1135
Number of pages11
JournalExperimental Cell Research
Volume314
Issue number5
DOIs
StatePublished - Mar 10 2008

Keywords

  • Muscle injury
  • Muscle repair
  • Sca-1
  • Skeletal muscle
  • Stem cell

ASJC Scopus subject areas

  • Cell Biology

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