Sca-1-expressing nonmyogenic cells contribute to fibrosis in aged skeletal muscle.
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.
College of Health Sciences, University of Kentucky, 900 S. Limestone, CTW 105, Lexington, KY 40536-0200, USA.
Mats
M
Hidestrand
Sonia
S
Richards-Malcolm
Catherine M
CM
Gurley
Greg
G
Nolen
Barry
B
Grimes
Amanda
A
Waterstrat
Gary Van
GV
Zant
Charlotte A
CA
Peterson
D000375:Aging / Q000473:pathology*; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D008811:Mice, Inbred DBA; D018482:Muscle, Skeletal / Q000473:pathology* / Q000502:physiology; D017570:MyoD Protein; D012038:Regeneration / Q000502:physiology
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D017570:MyoD Protein; D017493:Leukocyte Common Antigens