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Disintegration of the NuRD complex in primary human muscle stem cells in critical illness myopathy

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Item Type:Article
Title:Disintegration of the NuRD complex in primary human muscle stem cells in critical illness myopathy
Creators Name:Schneider, J. and Sundaravinayagam, D. and Blume, A. and Marg, A. and Grunwald, S. and Metzler, E. and Escobar, H. and Müthel, S. and Wang, H. and Wollersheim, T. and Weber-Carstens, S. and Akalin, A. and Di Virgilio, M. and Tursun, B. and Spuler, S.
Abstract:Critical illness myopathy (CIM) is an acquired, devastating, multifactorial muscle-wasting disease with incomplete recovery. The impact on hospital costs and permanent loss of quality of life is enormous. Incomplete recovery might imply that the function of muscle stem cells (MuSC) is impaired. We tested whether epigenetic alterations could be in part responsible. We characterized human muscle stem cells (MuSC) isolated from early CIM and analyzed epigenetic alterations (CIM n = 15, controls n = 21) by RNA-Seq, immunofluorescence, analysis of DNA repair, and ATAC-Seq. CIM-MuSC were transplanted into immunodeficient NOG mice to assess their regenerative potential. CIM-MuSC exhibited significant growth deficits, reduced ability to differentiate into myotubes, and impaired DNA repair. The chromatin structure was damaged, as characterized by alterations in mRNA of histone 1, depletion or dislocation of core proteins of nucleosome remodeling and deacetylase complex, and loosening of multiple nucleosome-spanning sites. Functionally, CIM-MuSC had a defect in building new muscle fibers. Further, MuSC obtained from the electrically stimulated muscle of CIM patients was very similar to control MuSC, indicating the impact of muscle contraction in the onset of CIM. CIM not only affects working skeletal muscle but has a lasting and severe epigenetic impact on MuSC.
Keywords:Epigenetic, Muscle Stem Cell, Critical Illness, Histone 1, Animals, Mice
Source:International Journal of Molecular Sciences
Page Range:2772
Date:1 February 2023
Official Publication:https://doi.org/10.3390/ijms24032772
PubMed:View item in PubMed

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