Int J Biol Sci 2019; 15(1):34-43. doi:10.7150/ijbs.28879
E-cadherin is Required for the Homeostasis of Lgr5+ Gastric Antral Stem Cells
1. State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences, Beijing Institute of Lifeomics, Beijing 102206, China.
2. State Key Laboratory of Membrane Biology, College of Life Sciences, Tsinghua University, Beijing, 100084, China.
Tang Y, Yang G, Zhang J, Li X, Zhang C, Wang Y, Xu J, Chen Y, Teng Y, Yang X. E-cadherin is Required for the Homeostasis of Lgr5+ Gastric Antral Stem Cells. Int J Biol Sci 2019; 15(1):34-43. doi:10.7150/ijbs.28879. Available from http://www.ijbs.com/v15p0034.htm
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.
Keywords: E-cadherin, gastric epithelium, Lgr5+ stem cells, apoptosis, homeostasis