Single cell RNA-seq reveals profound transcriptional similarity between Barrett’s esophagus and esophageal glands

Abstract

AbstractBarrett’s esophagus is a precursor of esophageal adenocarcinoma. In this common condition, squamous epithelium in the esophagus is replaced by columnar epithelium in response to acid reflux. Barrett’s esophagus is highly heterogeneous and its relationships to normal tissues are unclear. We investigated the cellular complexity of Barrett’s esophagus and the upper gastrointestinal tract using RNA-sequencing of 2895 single cells from multiple biopsies from four patients with Barrett’s esophagus and two patients without esophageal pathology. We found that uncharacterised cell populations in Barrett’s esophagus, marked by LEFTY1 and OLFM4, exhibit a profound transcriptional overlap with a subset of esophageal cells, but not with gastric or duodenal cells. Additionally, SPINK4 and ITLN1 mark cells that precede morphologically identifiable goblet cells in colon and Barrett’s esophagus, potentially aiding the identification of metaplasia. Our findings reveal striking transcriptional relationships between normal tissue populations and cells in a premalignant condition, with implications for clinical practice.