Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging.

ABSTRACT: To understand the molecular features underlying stem cell aging, we established intestinal epithelial organoids derived from both young and aged mice and investigated alterations in their senescence and epigenetic status. Senescence-related changes including accumulation of senescence-associated β-galactosidase and up-regulation of Cdkn1a (p21) by DNA demethylation were observed in intestinal epithelial organoids derived from aged mice. We also demonstrated that the important stem cell marker Lgr5 was epigenetically silenced by trimethylation of histone H3 lysine 27, inducing suppression of Wnt signaling and a decrease of cell proliferation in organoids from aged mice. We further treated intestinal epithelial organoids from aged mice with nicotinamide mononucleotide (N

SUBMITTER: Uchida R 

PROVIDER: S-EPMC6279747 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature