TY - JOUR
T1 - High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells
AU - Beumer, Joep
AU - Puschhof, Jens
AU - Bauzá-Martinez, Julia
AU - Martínez-Silgado, Adriana
AU - Elmentaite, Rasa
AU - James, Kylie R
AU - Ross, Alexander
AU - Hendriks, Delilah
AU - Artegiani, Benedetta
AU - Busslinger, Georg A
AU - Ponsioen, Bas
AU - Andersson-Rolf, Amanda
AU - Saftien, Aurelia
AU - Boot, Charelle
AU - Kretzschmar, Kai
AU - Geurts, Maarten H
AU - Bar-Ephraim, Yotam E
AU - Pleguezuelos-Manzano, Cayetano
AU - Post, Yorick
AU - Begthel, Harry
AU - van der Linden, Franka
AU - Lopez-Iglesias, Carmen
AU - van de Wetering, Willine J
AU - van der Linden, Reinier
AU - Peters, Peter J
AU - Heck, Albert J R
AU - Goedhart, Joachim
AU - Snippert, Hugo
AU - Zilbauer, Matthias
AU - Teichmann, Sarah A
AU - Wu, Wei
AU - Clevers, Hans
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/6/11
Y1 - 2020/6/11
N2 - Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.
AB - Enteroendocrine cells (EECs) sense intestinal content and release hormones to regulate gastrointestinal activity, systemic metabolism, and food intake. Little is known about the molecular make-up of human EEC subtypes and the regulated secretion of individual hormones. Here, we describe an organoid-based platform for functional studies of human EECs. EEC formation is induced in vitro by transient expression of NEUROG3. A set of gut organoids was engineered in which the major hormones are fluorescently tagged. A single-cell mRNA atlas was generated for the different EEC subtypes, and their secreted products were recorded by mass-spectrometry. We note key differences to murine EECs, including hormones, sensory receptors, and transcription factors. Notably, several hormone-like molecules were identified. Inter-EEC communication is exemplified by secretin-induced GLP-1 secretion. Indeed, individual EEC subtypes carry receptors for various EEC hormones. This study provides a rich resource to study human EEC development and function.
KW - enteroendocrine cell
KW - organoids
KW - fluorescent tagging
KW - CRISPR-mediated knockin
KW - hormone
KW - proteomics
KW - secretomics
KW - single-cell atlas
KW - intestine
KW - human
U2 - 10.1016/j.cell.2020.04.036
DO - 10.1016/j.cell.2020.04.036
M3 - Article
C2 - 32407674
SN - 0092-8674
VL - 181
SP - 1291
EP - 1306
JO - Cell
JF - Cell
IS - 6
ER -