A human Barrett’s esophagus organoid system reveals epithelial-mesenchymal plasticity induced by acid and bile salts

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.