METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell.

ABSTRACT: The development and homeostasis of intestinal epithelium are mediated by actively proliferating Lgr5+ stem cells, which possess a remarkable self-renewal and differentiation capacity. Recently, our study demonstrated that N6-methyladenosine (m6A) methylation was essential for the survival of colonic stem cells. Here, we show that methyltransferase-like 3 (METTL3) expression is downregulated in the colon mucosa in ulcerative colitis (UC) patients and strongly associated with the differentiation and maturation of goblet cells during inflammation. In mice, depletion of Mettl3 significantly inhibits the self-renewal and differentiation of Lgr5+ stem cells, especially the differentiation and maturation of goblet cells, resulting in intestinal dysplasia and spontaneous inflammation. Mechanistica

SUBMITTER: Ding C 

PROVIDER: S-EPMC12309382 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature