The satellite cell niche regulates the balance between myoblast differentiation and self-renewal via p53

Satellite cells (SCs) are adult muscle stem cells residing in a specialised niche that regulates SC homeostasis. How niche-generated signals integrate to regulate gene expression in SC-derived myoblasts, is poorly understood. We undertook an unbiased approach to study the effect of the SC niche on SC-derived myoblast transcriptional regulation and identified the tumour suppressor p53 as a key player in the regulation of myoblast quiescence. After activation and proliferation, a subpopulation of myoblasts cultured in the presence of the niche upregulates p53 and fails to differentiate. When SC self-renewal is modelled ex vivo in a reserve cell assay, myoblasts treated with Nutlin-3, which increases p53 levels in the cell, fail to differentiate and instead become quiescent. Since both these effects of Nutlin-3 are rescued by siRNA-mediated p53 knockdown we conclude that a tight control of p53 levels in myoblasts regulate the balance between differentiation and return to quiescence. Myofibres were extracted from Male mice and 48h and 72h after isolation collected washed and characterized on Agilent microarrays.