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The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53
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 satel...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918193/ https://www.ncbi.nlm.nih.gov/pubmed/29429962 http://dx.doi.org/10.1016/j.stemcr.2018.01.007 |
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author | Flamini, Valentina Ghadiali, Rachel S. Antczak, Philipp Rothwell, Amy Turnbull, Jeremy E. Pisconti, Addolorata |
author_facet | Flamini, Valentina Ghadiali, Rachel S. Antczak, Philipp Rothwell, Amy Turnbull, Jeremy E. Pisconti, Addolorata |
author_sort | Flamini, Valentina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5918193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59181932018-04-27 The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 Flamini, Valentina Ghadiali, Rachel S. Antczak, Philipp Rothwell, Amy Turnbull, Jeremy E. Pisconti, Addolorata Stem Cell Reports Article 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. Elsevier 2018-02-08 /pmc/articles/PMC5918193/ /pubmed/29429962 http://dx.doi.org/10.1016/j.stemcr.2018.01.007 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Flamini, Valentina Ghadiali, Rachel S. Antczak, Philipp Rothwell, Amy Turnbull, Jeremy E. Pisconti, Addolorata The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title | The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title_full | The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title_fullStr | The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title_full_unstemmed | The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title_short | The Satellite Cell Niche Regulates the Balance between Myoblast Differentiation and Self-Renewal via p53 |
title_sort | satellite cell niche regulates the balance between myoblast differentiation and self-renewal via p53 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918193/ https://www.ncbi.nlm.nih.gov/pubmed/29429962 http://dx.doi.org/10.1016/j.stemcr.2018.01.007 |
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