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

Georg A Busslinger, Bas L A Weusten, Auke Bogte, Harry Begthel, Lodewijk A A Brosens, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

133 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)108819
JournalCell Reports
Volume34
Issue number10
DOIs
Publication statusPublished - 09 Mar 2021

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