Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of alpha7 integrin-expressing myoblasts.
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.
Epting
Conrad L
CL
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0130, USA.
López
Javier E
JE
Pedersen
Anissa
A
Brown
Courtney
C
Spitz
Paul
P
Ursell
Philip C
PC
Bernstein
Harold S
HS
D000818:Animals; D015703:Antigens, CD; D000950:Antigens, Ly / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D039001:Integrin alpha Chains; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology*; D012038:Regeneration
D015703:Antigens, CD; D000950:Antigens, Ly; D039001:Integrin alpha Chains; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C085725:integrin alpha7