Transcriptional landscape of BE disease progression

Our mouse model of BE in which overexpression of IL-1b in the squamous esophagus induces chronic inflammation leads to metaplasia and dysplasia at the squamo-columnar junction (SCJ) in the mouse gastro-esophageal junction resembles the human disease. Adult L2-IL1b mice were employed to investigate changes to the transcriptional landscape at the SCJ during disease progression from BE to EAC following pharmaceutical or genetic perturbations of interest to BE biology. Barrett Esophagus (BE) is a risk factor for the development of esophageal adenocarcinoma (EAC). Disease progression, however, is not well understood. Here, we utilized our IL-1b mouse model of BE to study the impact of following risk factors on progression of BE to EAC: high fat diet (HFD) and overexpression of IL-8, modulations of the bile acid receptor FXR, modifications of Notch signaling in intestinal Lgr5-positive intestinal stem cells and modifications of Notch signaling in intestinal Dclk1-positive post-mitotic tuft cells.