Human gastrointestinal epithelia of the esophagus, stomach and duodenum resolved at single-cell resolution

The upper gastrointestinal tract consisting of the esophagus, stomach and duodenum controls food transport, digestion, nutrient uptake and hormone production. By single-cell analysis of healthy epithelia of these human organs, we molecularly defined their distinct cell types. We identified a quiescent COL17A1high stem/progenitor cell population within the basal cell layer of the esophagus and detected substantial gene expression differences between identical cell types of the human and mouse stomach. Selective and high expression of BEST4, CFTR, guanylin and uroguanylin identified the rare duodenal BCHE cells, which likely mediate high-volume fluid secretion due to continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Unexpectedly, the previously uncharacterized serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from the duodenal enterochromaffin cells. We furthermore discovered that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express luteinizing hormone, not previously seen in enteroendocrine cells. single cell sequencing (SORT-seq) on gastric epithelium of C57BL/6 mice