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Sreenivasan K, Rodríguez-delaRosa A, Kim J, et al. CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. Stem Cell Reports. 2021;16(9):2089-2098doi: 10.1016/j.stemcr.2021.07.022.
Sreenivasan, K., Rodríguez-delaRosa, A., Kim, J., Mesquita, D., Segalés, J., Arco, P. G., Espejo, I., Ianni, A., Di Croce, L., Relaix, F., Redondo, J. M., Braun, T., Serrano, A. L., Perdiguero, E., & Muñoz-Cánoves, P. (2021). CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. Stem cell reports, 16(9), 2089-2098. https://doi.org/10.1016/j.stemcr.2021.07.022
Sreenivasan, Krishnamoorthy, et al. "CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration." Stem cell reports vol. 16,9 (2021): 2089-2098. doi: https://doi.org/10.1016/j.stemcr.2021.07.022
Sreenivasan K, Rodríguez-delaRosa A, Kim J, Mesquita D, Segalés J, Arco PG, Espejo I, Ianni A, Di Croce L, Relaix F, Redondo JM, Braun T, Serrano AL, Perdiguero E, Muñoz-Cánoves P. CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration. Stem Cell Reports. 2021 Sep 14;16(9):2089-2098. doi: 10.1016/j.stemcr.2021.07.022. Epub 2021 Aug 26. PMID: 34450038; PMCID: PMC8452531.
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Stem Cell Reports. 2021 Sep 14;16(9):2089-2098. doi: 10.1016/j.stemcr.2021.07.022. Epub 2021 Aug 26.

CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration.

Stem cell reports

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

Affiliations

  1. Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
  2. Department of Experimental & Health Sciences, University Pompeu Fabra (UPF), CIBERNED, 08003 Barcelona, Spain.
  3. Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; German Center for Cardiovascular Research (DZHK), Rhine Main, Germany.
  4. Institute of Rare Diseases Research, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain; Gene Regulation in Cardiovascular Remodelling & Inflammation Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
  5. Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, 08003 Barcelona, Spain.
  6. Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, 08003 Barcelona, Spain; Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; ICREA, 08010 Barcelona, Spain.
  7. Univ Paris Est Creteil, INSERM, EnvA, EFS, AP-HP, IMRB, F-94010 Creteil, France.
  8. Gene Regulation in Cardiovascular Remodelling & Inflammation Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
  9. Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; German Center for Cardiovascular Research (DZHK), Rhine Main, Germany; German Center for Lung Research (DZL), Giessen, Germany.
  10. Department of Experimental & Health Sciences, University Pompeu Fabra (UPF), CIBERNED, 08003 Barcelona, Spain. Electronic address: [email protected].
  11. Department of Experimental & Health Sciences, University Pompeu Fabra (UPF), CIBERNED, 08003 Barcelona, Spain. Electronic address: [email protected].
  12. Department of Experimental & Health Sciences, University Pompeu Fabra (UPF), CIBERNED, 08003 Barcelona, Spain; ICREA, 08010 Barcelona, Spain; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain. Electronic address: [email protected].

PMID: 34450038 PMCID: PMC8452531 DOI: 10.1016/j.stemcr.2021.07.022

Abstract

Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, 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 Chd4 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 Chd4. Thus, CHD4 ensures that a transcriptional program that safeguards satellite cell identity during muscle regeneration is maintained. Given the therapeutic potential of muscle stem cells in diverse neuromuscular pathologies, CHD4 constitutes an attractive target for satellite cell-based therapies.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Chd4; NuRD; lineage maintenance; muscle stem cell; regeneration; satellite cells; skeletal muscle

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