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 define their distinct cell types. We identify a quiescent COL17A1(high) KRT15(high) stem/progenitor cell population in the most basal cell layer of the esophagus and detect substantial gene expression differences between identical cell types of the human and mouse stomach. Selective expression of BEST4, CFTR, guanylin, and uroguanylin identifies a rare duodenal cell type, referred to as BCHE cell, which likely mediates high-volume fluid secretion because of continual activation of the CFTR channel by guanylin/uroguanylin-mediated autocrine signaling. Serotonin-producing enterochromaffin cells in the antral stomach significantly differ in gene expression from duodenal enterochromaffin cells. We, furthermore, discover that the histamine-producing enterochromaffin-like cells in the oxyntic stomach express the luteinizing hormone, yet another member of the enteroendocrine hormone family.

Automated summary

The upper gastrointestinal tract, including the esophagus, stomach, and duodenum, controls different functions such as food transport, digestion, and hormone production. Through single-cell analysis, distinct cell types have been identified in these organs, with specific populations like quiescent stem/progenitor cells and rare BCHE cells in the esophagus and duodenum respectively. Gene expression varies significantly between identical cell types in different organs, and there are unique cell types like serotonin-producing enterochromaffin cells and histamine-producing enterochromaffin-like cells that express additional hormones such as luteinizing hormone.