CHD4 Ensures Stem Cell Lineage Fidelity During Skeletal Muscle Regeneration

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Aug 27

PMID 34450038

Citations 8

Authors

Krishnamoorthy Sreenivasan

Alejandra Rodriguez-delaRosa

Johnny Kim

Diana Mesquita

Jessica Segales

Pablo Gomez-Del Arco

Isabel Espejo

Alessandro Ianni

Luciano Di Croce

Frederic Relaix

Juan Miguel Redondo

Thomas Braun

Antonio L Serrano

Eusebio Perdiguero

Pura Munoz-Canoves

Affiliations

Soon will be listed here.

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.

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