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. 2020 May 7;S0092-8674(20)30501-8.
doi: 10.1016/j.cell.2020.04.036. Online ahead of print.

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

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High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Joep Beumer et al. Cell. .

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.

Keywords: CRISPR-mediated knockin; enteroendocrine cell; fluorescent tagging; hormone; human; intestine; organoids; proteomics; secretomics; single-cell atlas.

Conflict of interest statement

Declaration of Interests H.C. is inventor on several patents related to organoid technology; his full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. is founder of OrganoidZ, which employs organoids for drug development. J.B., J.P., and H.C. are inventors on patents related to this work.

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