Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle

Mats Hidestrand, Sonia Richards-Malcolm, Catherine M. Gurley, Greg Nolen, Barry Grimes, Amanda Waterstrat, Gary Van Zant, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

We report an age-dependent increase in nonimmunohematopoietic cells (CD45neg) in regenerating muscle characterized by high stem-cell antigen (Sca-1) expression. In aged regenerating muscle, only 14% of these CD45negSca-1pos cells express MyoD, whereas 82% of CD45negSca-1pos cells are MyoDpos in young adult muscle. In vitro, CD45negMyoDnegSca-1pos cells overexpress fibrosis-promoting genes, potentially controlled by Wnt2. The cells are proliferative, nonmyogenic, and nonadipogenic, and arise in clonally derived myoblast cultures from aged mice. MyoDneg Sca-1pos nonmyogenic cells also emerge in C2C12 myoblast cultures at late passage. Both in vitro and in vivo studies suggest that MyoDnegSca-1pos cells from aged muscle are more susceptible to apoptosis than myoblasts, which may contribute to depletion of the satellite cell pool. Thus, with age, a subset of myoblasts takes on an altered phenotype, which is marked by high Sca-1 expression. These cells do not participate in muscle regeneration, and instead may contribute to muscle fibrosis in aged muscle.

Original languageEnglish
Pages (from-to)566-579
Number of pages14
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume63
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Aging
  • Fibrosis
  • Muscle stem cells
  • Sca-1
  • Skeletal muscle regeneration

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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