Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of α7 integrin-expressing myoblasts

Conrad L. Epting; Javier E. López; Anissa Pedersen; Courtney Brown; Paul Spitz; Philip C. Ursell; Harold S. Bernstein

doi:10.1016/j.yexcr.2007.11.010

Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of α7 integrin-expressing myoblasts

Conrad L. Epting, Javier E. López, Anissa Pedersen, Courtney Brown, Paul Spitz, Philip C. Ursell, Harold S. Bernstein^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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)
Pages (from-to)	1125-1135
Number of pages	11
Journal	Experimental Cell Research
Volume	314
Issue number	5
DOIs	https://doi.org/10.1016/j.yexcr.2007.11.010
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

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10.1016/j.yexcr.2007.11.010

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title = "Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of α7 integrin-expressing myoblasts",

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.",

keywords = "Muscle injury, Muscle repair, Sca-1, Skeletal muscle, Stem cell",

author = "Epting, {Conrad L.} and L{\'o}pez, {Javier E.} and Anissa Pedersen and Courtney Brown and Paul Spitz and Ursell, {Philip C.} and Bernstein, {Harold S.}",

note = "Funding Information: 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. ",

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AU - Spitz, Paul

AU - Ursell, Philip C.

AU - Bernstein, Harold S.

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N2 - 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.

AB - 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.

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Stem cell antigen-1 regulates the tempo of muscle repair through effects on proliferation of α7 integrin-expressing myoblasts

Abstract

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