CCAAT/Enhancer Binding Protein Beta is Expressed in Satellite Cells and Controls Myogenesis

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 durin...

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Bibliographic Details
Published in:	Stem cells (Dayton, Ohio) Vol. 30; no. 12; pp. 2619 - 2630
Main Authors:	Marchildon, François, Lala, Neena, Li, Grace, St-Louis, Catherine, Lamothe, Daniel, Keller, Charles, Wiper-Bergeron, Nadine
Format:	Journal Article
Language:	English
Published:	Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2012 Oxford University Press
Subjects:	Animals CCAAT-enhancer binding protein beta CCAAT-Enhancer-Binding Protein-beta - biosynthesis Cell Differentiation - physiology Cells, Cultured Female Mice Mice, Inbred C57BL Muscle development Muscle Development - physiology Muscle, Skeletal - cytology Muscle, Skeletal - metabolism MyoD Protein - metabolism MyoD1 myogenic differentiation protein Proteins Satellite cells Satellite Cells, Skeletal Muscle - cytology Satellite Cells, Skeletal Muscle - metabolism Satellites Skeletal muscle
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Summary:	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
Bibliography:	istex:FC058317E1F61464C0A4E47D4DBEF396ABBB69AF Cancer Research Society with funds from the University of Ottawa's Research Development Program Disclosure of potential conflicts of interest is found at the end of this article. Canadian Institutes of Health Research (CIHR) Ontario Graduate Scholarship ArticleID:STEM1248 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. First published online in STEM CELLSEXPRESS November 7, 2012. ark:/67375/WNG-7T6RGTLH-3 First published online in S Telephone: 613‐562‐5800, ext. 8176; Fax: 613‐562‐5687 C XPRESS November 7, 2012. E TEM ELLS ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1066-5099 1549-4918
DOI:	10.1002/stem.1248