Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle. J Gerontol A Biol Sci Med Sci 2008 Jun;63(6):566-79
Date
06/19/2008Pubmed ID
18559630Pubmed Central ID
PMC2755567DOI
10.1093/gerona/63.6.566Scopus ID
2-s2.0-50849116835 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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-1(pos) 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.
Author List
Hidestrand M, Richards-Malcolm S, Gurley CM, Nolen G, Grimes B, Waterstrat A, Zant GV, Peterson CAMESH terms used to index this publication - Major topics in bold
AgingAnimals
Antigens, Ly
Cells, Cultured
Female
Fibrosis
Leukocyte Common Antigens
Membrane Proteins
Mice
Mice, Inbred DBA
Muscle, Skeletal
MyoD Protein
Regeneration
