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CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration

Sreenivasan, Krishnamoorthy; Rodríguez-delaRosa, Alejandra; Johnny, Kim; Mesquita, Diana; Segalés, Jessica; Gomez-del Arco, Pablo; Espejo, Isabel; Ianni, Alessandro; Di Croce, Luciano; Relaix, Frederic; Redondo, Juan Miguel; Braun, Thomas; Serrano, Antonio L; Perdiguero, Eusebio; Muñoz-Cánoves, Pura

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    <dct:description>&lt;p&gt;&lt;strong&gt;Summary&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler&amp;nbsp;&lt;a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/chd4"&gt;CHD4&lt;/a&gt;, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We show that conditional deletion of the&amp;nbsp;&lt;em&gt;Chd4&lt;/em&gt;&amp;nbsp;gene in satellite cells results in failure to regenerate muscle after injury. This defect is principally associated with increased stem cell plasticity and lineage infidelity during the expansion of satellite cells, caused by de-repression of non-muscle-cell lineage genes in the absence of&amp;nbsp;&lt;em&gt;Chd4&lt;/em&gt;. Thus, CHD4 ensures that a transcriptional program that safeguards satellite cell identity during&amp;nbsp;&lt;a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/muscle-regeneration"&gt;muscle regeneration&lt;/a&gt;&amp;nbsp;is maintained. Given the therapeutic potential of muscle stem cells in diverse neuromuscular pathologies, CHD4 constitutes an attractive target for satellite cell-based therapies.&lt;/p&gt;</dct:description>
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Publication date:
August 26, 2021
DOI:
10.1016/j.stemcr.2021.07.022
Published in:
Stem Cell Reports: 16 pp. 2089-2098 (9).
Grants:
European Commission:
  • UPGRADE - Unlocking Precision Gene Therapy (825825)
Communities:
License (for files):
Creative Commons Attribution 4.0 International

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