Abstract
Upon injury, muscle satellite cells become activated and produce skeletal muscle precursors that engage in myogenesis. We demonstrate that the transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is expressed in the satellite cells of healthy muscle. C/EBPβ expression is regulated during myogenesis such that C/EBPβ is rapidly and massively downregulated upon induction to differentiate. Furthermore, persistent expression of C/EBPβ in myoblasts potently inhibits differentiation at least in part through the inhibition of MyoD protein function and stability. As a consequence, myogenic factor expression, myosin heavy chain expression, and fusogenic activity were reduced in C/EBPβ-overexpressing cells. Using knockout models, we demonstrate that loss of Cebpb expression in satellite cells results in precocious differentiation of myoblasts in growth conditions and greater cell fusion upon differentiation. In vivo, loss of Cebpb expression in satellite cells resulted in larger muscle fiber cross-sectional area and improved repair after muscle injury. Our results support the notion that C/EBPβ inhibits myogenic differentiation and that its levels must be reduced to allow for activation of MyoD target genes and the progression of differentiation.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2619-2630 |
| Number of pages | 12 |
| Journal | Stem Cells |
| Volume | 30 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2012 |
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Keywords
- CCAAT-enhancer binding protein beta
- Muscle development
- MyoD1 myogenic differentiation protein
- Satellite cells
- Skeletal muscle
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Molecular Medicine
Cite this
CCAAT/enhancer binding protein beta is expressed in satellite cells and controls myogenesis. / Marchildon, François; Lala, Neena; Li, Grace; St.-Louis, Catherine; Lamothe, Daniel; Keller, Charles; Wiper-Bergeron, Nadine.
In: Stem Cells, Vol. 30, No. 12, 12.2012, p. 2619-2630.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CCAAT/enhancer binding protein beta is expressed in satellite cells and controls myogenesis
AU - Marchildon, François
AU - Lala, Neena
AU - Li, Grace
AU - St.-Louis, Catherine
AU - Lamothe, Daniel
AU - Keller, Charles
AU - Wiper-Bergeron, Nadine
PY - 2012/12
Y1 - 2012/12
N2 - Upon injury, muscle satellite cells become activated and produce skeletal muscle precursors that engage in myogenesis. We demonstrate that the transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is expressed in the satellite cells of healthy muscle. C/EBPβ expression is regulated during myogenesis such that C/EBPβ is rapidly and massively downregulated upon induction to differentiate. Furthermore, persistent expression of C/EBPβ in myoblasts potently inhibits differentiation at least in part through the inhibition of MyoD protein function and stability. As a consequence, myogenic factor expression, myosin heavy chain expression, and fusogenic activity were reduced in C/EBPβ-overexpressing cells. Using knockout models, we demonstrate that loss of Cebpb expression in satellite cells results in precocious differentiation of myoblasts in growth conditions and greater cell fusion upon differentiation. In vivo, loss of Cebpb expression in satellite cells resulted in larger muscle fiber cross-sectional area and improved repair after muscle injury. Our results support the notion that C/EBPβ inhibits myogenic differentiation and that its levels must be reduced to allow for activation of MyoD target genes and the progression of differentiation.
AB - Upon injury, muscle satellite cells become activated and produce skeletal muscle precursors that engage in myogenesis. We demonstrate that the transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is expressed in the satellite cells of healthy muscle. C/EBPβ expression is regulated during myogenesis such that C/EBPβ is rapidly and massively downregulated upon induction to differentiate. Furthermore, persistent expression of C/EBPβ in myoblasts potently inhibits differentiation at least in part through the inhibition of MyoD protein function and stability. As a consequence, myogenic factor expression, myosin heavy chain expression, and fusogenic activity were reduced in C/EBPβ-overexpressing cells. Using knockout models, we demonstrate that loss of Cebpb expression in satellite cells results in precocious differentiation of myoblasts in growth conditions and greater cell fusion upon differentiation. In vivo, loss of Cebpb expression in satellite cells resulted in larger muscle fiber cross-sectional area and improved repair after muscle injury. Our results support the notion that C/EBPβ inhibits myogenic differentiation and that its levels must be reduced to allow for activation of MyoD target genes and the progression of differentiation.
KW - CCAAT-enhancer binding protein beta
KW - Muscle development
KW - MyoD1 myogenic differentiation protein
KW - Satellite cells
KW - Skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=84870335301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870335301&partnerID=8YFLogxK
U2 - 10.1002/stem.1248
DO - 10.1002/stem.1248
M3 - Article
C2 - 23034923
AN - SCOPUS:84870335301
VL - 30
SP - 2619
EP - 2630
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 12
ER -