| Literature DB >> 32407674 |
Joep Beumer1, Jens Puschhof1, Julia Bauzá-Martinez2, Adriana Martínez-Silgado1, Rasa Elmentaite3, Kylie R James3, Alexander Ross4, Delilah Hendriks1, Benedetta Artegiani1, Georg A Busslinger1, Bas Ponsioen5, Amanda Andersson-Rolf1, Aurelia Saftien1, Charelle Boot1, Kai Kretzschmar1, Maarten H Geurts1, Yotam E Bar-Ephraim1, Cayetano Pleguezuelos-Manzano1, Yorick Post1, Harry Begthel1, Franka van der Linden6, Carmen Lopez-Iglesias7, Willine J van de Wetering8, Reinier van der Linden1, Peter J Peters7, Albert J R Heck2, Joachim Goedhart6, Hugo Snippert5, Matthias Zilbauer9, Sarah A Teichmann10, Wei Wu2, Hans Clevers11.
Abstract
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.Entities:
Keywords: CRISPR-mediated knockin; enteroendocrine cell; fluorescent tagging; hormone; human; intestine; organoids; proteomics; secretomics; single-cell atlas
Year: 2020 PMID： 32407674 DOI： 10.1016/j.cell.2020.04.036
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582