beta-Catenin promotes self-renewal of skeletal-muscle satellite cells.
Satellite cells are the resident stem cells of adult skeletal muscle. As with all stem cells, how the choice between self-renewal or differentiation is controlled is central to understanding their function. Here, we have explored the role of beta-catenin in determining the fate of myogenic satellite cells. Satellite cells express beta-catenin, and expression is maintained as they activate and undergo proliferation. Constitutive retroviral-driven expression of wild-type or stabilised beta-catenin results in more satellite cells expressing Pax7 without any MyoD -- therefore, adopting the self-renewal pathway, with fewer cells undergoing myogenic differentiation. Similarly, preventing the degradation of endogenous beta-catenin by inhibiting GSK3beta activity also results in more Pax7-positive-MyoD-negative (Pax7(+)MyoD(-)) satellite-cell progeny. Consistent with these observations, downregulation of beta-catenin using small interfering RNA (siRNA) reduced the proportion of satellite cells that express Pax7 and augmented myogenic differentiation after mitogen withdrawal. Since a dominant-negative version of beta-catenin had the same effect as silencing beta-catenin using specific siRNA, beta-catenin promotes self-renewal via transcriptional control of target genes. Thus, beta-catenin signalling in proliferating satellite cells directs these cells towards the self-renewal pathway and, so, contributes to the maintenance of this stem-cell pool in adult skeletal muscle.
Perez-Ruiz
Ana
A
King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, UK.
Ono
Yusuke
Y
Gnocchi
Viola F
VF
Zammit
Peter S
PS
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002459:Cell Fusion; D049109:Cell Proliferation; D020868:Gene Silencing; D051379:Mice; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051176:beta Catenin