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J Cell Sci. 2008 May 1;121(Pt 9):1373-82. doi: 10.1242/jcs.024885. Epub 2008 Apr 8.

beta-Catenin promotes self-renewal of skeletal-muscle satellite cells.

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  • 1King's College London, Randall Division of Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London, UK.

Abstract

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.

PMID:
18397993
DOI:
10.1242/jcs.024885
[PubMed - indexed for MEDLINE]
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