Science (New York, N.Y.)Oct 17, 2024

Identifying and testing sensors in human gut hormone-producing cells

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

CD200 serves as a pan-EEC surface marker for profiling enteroendocrine cells along the stomach-intestinal tract.

Enteroendocrine cells (EECs) secrete hormones that regulate various physiological processes.
Differentiation of stomach EECs complements existing intestinal organoid protocols.
Loss-of-function mutations were generated in 22 receptors to study their role in hormone secretion.
Individual EEC sensors may influence the secretion of hormones like glucagon-like peptide 1 (GLP-1).
These EEC sensors could be potential pharmacological targets for appetite regulation and metabolic health.

Simplified

Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including the incretins glucagon-like peptide 1 (GLP-1) and gastric inhibitory protein (GIP), which regulate multiple physiological processes. Hormone release is controlled through metabolite-sensing proteins. Low expression, interspecies differences, and the existence of multiple EEC subtypes have posed challenges to the study of these sensors. We describe differentiation of stomach EECs to complement existing intestinal organoid protocols. CD200 emerged as a pan-EEC surface marker, allowing deep transcriptomic profiling from primary human tissue along the stomach-intestinal tract. We generated loss-of-function mutations in 22 receptors and subjected organoids to ligand-induced secretion experiments. We delineate the role of individual human EEC sensors in the secretion of hormones, including GLP-1. These represent potential pharmacological targets to influence appetite, bowel movement, insulin sensitivity, and mucosal immunity.

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Funding

Competing interests

Competing interests . HC is head of Roche’s Pharma Research and Early Development in Basel, Switzerland since March 2022. JB and HC are inventors on several patents related to organoid technology. HC’s full disclosure is given at https://www.uu.nl/staff/JCClevers/.

PubMed

Identifying and testing sensors in human gut hormone-producing cells

Abstract

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Funding

Competing interests

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Abstract

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Funding

Competing interests

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