Arsenic Directs Stem Cell Fate by Imparting Notch Signaling Into the Extracellular Matrix Niche.

ABSTRACT: Compromise of skeletal muscle metabolism and composition may underlie the etiology of cardiovascular and metabolic disease risk from environmental arsenic exposures. We reported that arsenic impairs muscle maintenance and regeneration by inducing maladaptive mitochondrial phenotypes in muscle stem cells (MuSC), connective tissue fibroblasts (CTF), and myofibers. We also found that arsenic imparts a dysfunctional memory in the extracellular matrix (ECM) that disrupts the MuSC niche and is sufficient to favor the expansion and differentiation of fibrogenic MuSC subpopulations. To investigate the signaling mechanisms involved in imparting a dysfunctional ECM, we isolated skeletal muscle tissue and CTF from mice exposed to 0 or 100 μg/l arsenic in their drinking water for 5 weeks. ECM elaborat

SUBMITTER: Anguiano T 

PROVIDER: S-EPMC7548290 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature