The satellite cell niche regulates the balance between myoblast differentiation and self-renewal via p53. 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. Overall design: Myofibres were extracted from Male mice and 48h and 72h after isolation collected washed and characterized on Agilent microarrays.