A human Barrett’s esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts
Qiuyang Zhang, Ajay Bansal, Kerry B. Dunbar, Yan Chang, Jianning Zhang, Uthra Balaji, Jinghua Gu, Xi Zhang, Eitan Podgaetz, Zui Pan, Stuart J. Spechler, Rhonda F. Souza
Abstract
Using Barrett's esophagus (BE) biopsies, we established organoids recapitulating key BE features. During early stages of organoid development, a GERD-like wound environment-induced features of epithelial-mesenchymal plasticity (EMP) in Barrett's progenitor cells, suggesting that reflux-induced EMP can enable Barrett's cells to migrate underneath squamous epithelium to form subsquamous intestinal metaplasia, a condition that may underlie Barrett's cancers that escape detection by endoscopic surveillance, and recurrences of Barrett's metaplasia following endoscopic eradication therapy.