High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Beumer, Joep, Puschhof, Jens, Bauzá-Martinez, Julia, Martínez-Silgado, Adriana, Elmentaite, Rasa, James, Kylie R., Ross, Alexander, Hendriks, Delilah, Artegiani, Benedetta, Busslinger, Georg A., Ponsioen, Bas, Andersson-Rolf, Amanda, Saftien, Aurelia, Boot, Charelle, Kretzschmar, Kai, Geurts, Maarten H., Bar-Ephraim, Yotam E., Pleguezuelos-Manzano, Cayetano, Post, Yorick, Begthel, Harry, van der Linden, Franka, Lopez-Iglesias, Carmen, van de Wetering, Willine J., van der Linden, Reinier, Peters, Peter J., Heck, Albert J.R., Goedhart, Joachim, Snippert, Hugo, Zilbauer, Matthias, Teichmann, Sarah A., Wu, Wei & Clevers, Hans

Published: 01/01/2020


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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