Open AccessCCAAT/Enhancer Binding Protein Beta is Expressed in Satellite Cells and Controls Myogenesis
Author(s) -
Marchildon François,
Lala Neena,
Li Grace,
StLouis Catherine,
Lamothe Daniel,
Keller Charles,
WiperBergeron Nadine
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1248
Subject(s) - myod , myogenesis , biology , myod protein , transcription factor , myocyte , cellular differentiation , myosin , microbiology and biotechnology , myogenic regulatory factors , myogenin , skeletal muscle , enhancer , endocrinology , genetics , gene
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. S TEM C ELLS 2012;30:2619–2630