-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 -catenin in determining the fate of myogenic satellite cells. Satellite cells express -catenin, and expression is maintained as they activate and undergo proliferation. Constitutive retroviral-driven expression of wild-type or stabilised -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 -catenin by inhibiting GSK3 activity also results in more Pax7-positive-MyoD-negative (Pax7⁺MyoD^-) satellite-cell progeny. Consistent with these observations, downregulation of -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 -catenin had the same effect as silencing -catenin using specific siRNA, -catenin promotes self-renewal via transcriptional control of target genes. Thus, -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.