Transcriptional reprogramming of skeletal muscle stem cells by the niche environment

Author:

Lazure Felicia,Farouni RickORCID,Sahinyan Korin,Blackburn Darren M.,Hernández-Corchado Aldo,Perron GabrielleORCID,Lu TianyuanORCID,Osakwe AdrienORCID,Ragoussis JiannisORCID,Crist Colin,Perkins Theodore J.ORCID,Jahani-Asl ArezuORCID,Najafabadi Hamed S.ORCID,Soleimani Vahab D.ORCID

Abstract

AbstractAdult stem cells are indispensable for tissue regeneration, but their function declines with age. The niche environment in which the stem cells reside plays a critical role in their function. However, quantification of the niche effect on stem cell function is lacking. Using muscle stem cells (MuSC) as a model, we show that aging leads to a significant transcriptomic shift in their subpopulations accompanied by locus-specific gain and loss of chromatin accessibility and DNA methylation. By combining in vivo MuSC transplantation and computational methods, we show that the expression of approximately half of all age-altered genes in MuSCs from aged male mice can be restored by exposure to a young niche environment. While there is a correlation between gene reversibility and epigenetic alterations, restoration of gene expression occurs primarily at the level of transcription. The stem cell niche environment therefore represents an important therapeutic target to enhance tissue regeneration in aging.

Funder

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

Stem Cell Network

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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