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

• Published in: International journal of biological sciences Vol. 15; no. 1; pp. 34 - 43
• Main Authors: Tang, Yuling, Yang, Guan, Zhang, Jinliang, Li, Xiubin, Zhang, Chong, Wang, Yanxiao, Xu, Jiaqian, Chen, Yeguang, Teng, Yan, Yang, Xiao
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2019; Ivyspring International Publisher
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Apoptosis - physiology; Cadherins - genetics; Cadherins - metabolism; Cells, Cultured; Clonal deletion; E-cadherin; Homeostasis; Homeostasis - genetics; Homeostasis - physiology; Mice; Microscopy, Confocal; Mutants; Organoids; p53 Protein; Phenotypes; Pyloric Antrum - cytology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Research Paper; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; gastric epithelium; homeostasis; apoptosis; E-cadherin; Lgr5+ stem cells
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.28879

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 and organoid growth . 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.