E-cadherin is Required for the Homeostasis of Lgr5⁺ Gastric Antral Stem Cells.

ABSTRACT: Lgr5-expressing stem cells contribute to the epithelial turnover of the gastric antrum. However, the mechanism controlling the homeostasis of Lgr5⁺ antral stem cells is not fully understood. Here, we demonstrate the key role of E-cadherin in the homeostasis of Lgr5⁺ gastric antral stem cells. The deletion of E-cadherin in these cells results in their apoptosis, thereby leading to a marked decrease in their number. A reduced Lgr5⁺ stem cell pool caused by the loss of E-cadherin impairs gastric antral epithelial homeostasis in vivo and organoid growth in vitro. Furthermore, p53 contributes to the apoptosis of Lgr5⁺ stem cells following E-cadherin loss, while the simultaneous deletion of p53 rescues the phenotype in E-cadherin mutants. Our study reveals the critical pro-survival function of E-cadherin in Lgr5⁺ gastric antral stem cells and the key role of the Lgr5⁺ stem cell pool in the maintenance of gastric epithelial homeostasis.

SUBMITTER: Tang Y 

PROVIDER: S-EPMC6329931 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature