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 language | English (US) |
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Pages (from-to) | 1125-1135 |
Number of pages | 11 |
Journal | Experimental Cell Research |
Volume | 314 |
Issue number | 5 |
DOIs | |
State | Published - Mar 10 2008 |
Funding
This work was supported by the Public Health Service grant HL062174 from NHLBI, an AHA Established Investigator Award, and funds from the Pollin Foundation to H.S.B. C.L.E. was supported by the AMSPDC Pediatric Scientist Development Program (Public Health Service grant HD004739) and the Pediatric Critical Care Scientist Development Program (Public Health Service grant HD047349). J.E.L. was supported by National Research Service Award HL062174 from NHLBI and is a research Scholar supported by the Sarnoff Cardiovascular Research Foundation.
Keywords
- Muscle injury
- Muscle repair
- Sca-1
- Skeletal muscle
- Stem cell
ASJC Scopus subject areas
- Cell Biology