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High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells
Author(s) -
Joep Beumer,
Jens Puschhof,
Julia BauzáMartinez,
Adriana Martínez-Silgado,
Rasa Elmentaite,
Kylie R. James,
Alexander Ross,
Delilah Hendriks,
Benedetta Artegiani,
Georg Busslinger,
Bas Ponsioen,
Amanda Andersson-Rolf,
Aurelia Saftien,
Charelle Boot,
Kai Kretzschmar,
Maarten H. Geurts,
Yotam E. BarEphraïm,
Cayetano PleguezuelosManzano,
Yorick Post,
Harry Begthel,
Franka H. van der Linden,
Carmen LópezIglesias,
Willine J. van de Wetering,
Reinier van der Linden,
Peter J. Peters,
Albert J. R. Heck,
Joachim Goedhart,
Hugo J.G. Snippert,
Matthias Zilbauer,
Sarah A. Teichmann,
Wei Wu,
Hans Clevers
Publication year - 2020
Publication title -
cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 26.304
H-Index - 776
eISSN - 1097-4172
pISSN - 0092-8674
DOI - 10.1016/j.cell.2020.04.036
Subject(s) - biology , enteroendocrine cell , hormone , secretin , organoid , microbiology and biotechnology , receptor , secretion , endocrine system , endocrinology , genetics
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.

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