The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53

Flamini, Valentina, Ghadiali, Rachel, Antczak, Philipp ORCID: 0000-0001-9600-7757, Rothwell, Amy, Turnbull, Jeremy ORCID: 0000-0002-1791-754X and Pisconti, A (2018) The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53. Stem Cell Reports, 10 (3). pp. 970-983.

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Abstract

Satellite cells are adult muscle stem cells residing in a specialized niche that regulates their homeostasis. How niche-generated signals integrate to regulate gene expression in satellite cell-derived myoblasts is poorly understood. We undertook an unbiased approach to study the effect of the satellite cell niche on satellite cell-derived myoblast transcriptional regulation and identified the tumor 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 satellite cell self-renewal is modeled 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 Nutlin-3 effects are rescued by small interfering RNA-mediated p53 knockdown, we conclude that a tight control of p53 levels in myoblasts regulates the balance between differentiation and return to quiescence.

Item Type:	Article
Uncontrolled Keywords:	satellite cells, muscle stem cells, niche, p53, satellite cell quiescence, self-renewal, asymmetric satellite cell division, gene expression regulation, differentiation, transctiptomics
Depositing User:	Symplectic Admin
Date Deposited:	22 Feb 2018 09:56
Last Modified:	19 Jan 2023 06:39
DOI:	10.1016/j.stemcr.2018.01.007
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3018317