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). 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: 30 Nov 2020 16:10
DOI: 10.1016/j.stemcr.2018.01.007
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3018317