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Tissue-Specific Stem Cells
Version of Record online: 27 NOV 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 12, pages 2619–2630, December 2012
How to Cite
Marchildon, F., Lala, N., Li, G., St-Louis, C., Lamothe, D., Keller, C. and Wiper-Bergeron, N. (2012), CCAAT/Enhancer Binding Protein Beta is Expressed in Satellite Cells and Controls Myogenesis. STEM CELLS, 30: 2619–2630. doi: 10.1002/stem.1248
F.M.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript; N.L., G.L., and D.L.: collection and assembly of data, data analysis and interpretation, and final approval of manuscript; C.S.: administrative support, collection and assembly of data, and final approval of manuscript; C.K.: provision of study materials, manuscript writing, and final approval of manuscript; N.W.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 7, 2012.
- Issue online: 27 NOV 2012
- Version of Record online: 27 NOV 2012
- Accepted manuscript online: 3 OCT 2012 03:16PM EST
- Manuscript Accepted: 4 AUG 2012
- Manuscript Received: 7 FEB 2012
- Canadian Institutes of Health Research (CIHR)
- Cancer Research Society with funds from the University of Ottawa's Research Development Program
- Ontario Graduate Scholarship
- Muscle development;
- Satellite cells;
- Skeletal muscle;
- MyoD1 myogenic differentiation protein;
- CCAAT-enhancer binding protein beta
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. STEM CELLS 2012;30:2619–2630