Description and functional validation of human enteroendocrine cell sensors

Joep Beumer; Maarten H. Geurts; Veerle Geurts; Amanda Andersson-Rolf; Ninouk Akkerman; Franziska Völlmy; Daniel Krueger; Georg A. Busslinger; Adriana Martínez-Silgado; Charelle Boot; Fjodor A. Yousef Yengej; Jens Puschhof; Wiline J. Van de Wetering; Kevin Knoops; Carmen López-Iglesias; Peter J. Peters; Judith A. Vivié; Dylan Mooijman; Johan H. van Es; Hans Clevers

doi:10.1126/science.adl1460

Description and functional validation of human enteroendocrine cell sensors

Joep Beumer^*, Maarten H. Geurts, Veerle Geurts, Amanda Andersson-Rolf, Ninouk Akkerman, Franziska Völlmy, Daniel Krueger, Georg A. Busslinger, Adriana Martínez-Silgado, Charelle Boot, Fjodor A. Yousef Yengej, Jens Puschhof, Wiline J. Van de Wetering, Kevin Knoops, Carmen López-Iglesias, Peter J. Peters, Judith A. Vivié, Dylan Mooijman, Johan H. van Es, Hans Clevers^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	341-348
Number of pages	8
Journal	Science
Volume	386
Issue number	6719
DOIs	https://doi.org/10.1126/science.adl1460
Publication status	Published - 18 Oct 2024

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Beumer, J., Geurts, M. H., Geurts, V., Andersson-Rolf, A., Akkerman, N., Völlmy, F., Krueger, D., Busslinger, G. A., Martínez-Silgado, A., Boot, C., Yousef Yengej, F. A., Puschhof, J., Van de Wetering, W. J., Knoops, K., López-Iglesias, C., Peters, P. J., Vivié, J. A., Mooijman, D., van Es, J. H., & Clevers, H. (2024). Description and functional validation of human enteroendocrine cell sensors. Science, 386(6719), 341-348. https://doi.org/10.1126/science.adl1460

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title = "Description and functional validation of human enteroendocrine cell sensors",

abstract = "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.",

author = "Joep Beumer and Geurts, {Maarten H.} and Veerle Geurts and Amanda Andersson-Rolf and Ninouk Akkerman and Franziska V{\"o}llmy and Daniel Krueger and Busslinger, {Georg A.} and Adriana Mart{\'i}nez-Silgado and Charelle Boot and {Yousef Yengej}, {Fjodor A.} and Jens Puschhof and {Van de Wetering}, {Wiline J.} and Kevin Knoops and Carmen L{\'o}pez-Iglesias and Peters, {Peter J.} and Vivi{\'e}, {Judith A.} and Dylan Mooijman and {van Es}, {Johan H.} and Hans Clevers",

note = "Publisher Copyright: {\textcopyright} 2024 the authors.",

year = "2024",

month = oct,

day = "18",

doi = "10.1126/science.adl1460",

language = "English",

volume = "386",

pages = "341--348",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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Beumer, J, Geurts, MH, Geurts, V, Andersson-Rolf, A, Akkerman, N, Völlmy, F, Krueger, D, Busslinger, GA, Martínez-Silgado, A, Boot, C, Yousef Yengej, FA, Puschhof, J, Van de Wetering, WJ, Knoops, K, López-Iglesias, C, Peters, PJ, Vivié, JA, Mooijman, D, van Es, JH & Clevers, H 2024, 'Description and functional validation of human enteroendocrine cell sensors', Science, vol. 386, no. 6719, pp. 341-348. https://doi.org/10.1126/science.adl1460

TY - JOUR

T1 - Description and functional validation of human enteroendocrine cell sensors

AU - Beumer, Joep

AU - Geurts, Maarten H.

AU - Geurts, Veerle

AU - Andersson-Rolf, Amanda

AU - Akkerman, Ninouk

AU - Völlmy, Franziska

AU - Krueger, Daniel

AU - Busslinger, Georg A.

AU - Martínez-Silgado, Adriana

AU - Boot, Charelle

AU - Yousef Yengej, Fjodor A.

AU - Puschhof, Jens

AU - Van de Wetering, Wiline J.

AU - Knoops, Kevin

AU - López-Iglesias, Carmen

AU - Peters, Peter J.

AU - Vivié, Judith A.

AU - Mooijman, Dylan

AU - van Es, Johan H.

AU - Clevers, Hans

PY - 2024/10/18

Y1 - 2024/10/18

N2 - 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.

AB - 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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U2 - 10.1126/science.adl1460

DO - 10.1126/science.adl1460

M3 - Article

C2 - 39418382

AN - SCOPUS:85206854141

SN - 0036-8075

VL - 386

SP - 341

EP - 348

JO - Science

JF - Science

IS - 6719

ER -

Description and functional validation of human enteroendocrine cell sensors

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