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

TLDR

The upper gastrointestinal tract, comprising esophagus, stomach, and duodenum, regulates food transport, digestion, nutrient absorption, and hormone production. This study uses single‑cell analysis of healthy human esophageal, gastric, and duodenal epithelia to molecularly define their distinct cell types. Single‑cell RNA sequencing was performed on healthy epithelia from these organs to map and characterize individual cell populations. We identified a quiescent COL17A1^high KRT15^high stem/progenitor population in the basal esophageal layer, revealed species‑specific gene expression differences in identical gastric cell types, discovered a rare duodenal BEST4/CFTR/guanylin/uroguanylin‑expressing BCHE cell likely mediating fluid secretion, noted distinct serotonin‑producing enterochromaffin cells between antral stomach and duodenum, and found luteinizing hormone expression in oxyntic stomach enterochromaffin‑like cells.

Abstract

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 COL17A1high KRT15high 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.