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. 2020 Jun 11;181(6):1291-1306.e19.
doi: 10.1016/j.cell.2020.04.036. Epub 2020 May 13.

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Joep Beumer  1 , Jens Puschhof  1 , Julia Bauzá-Martinez  2 , Adriana Martínez-Silgado  1 , Rasa Elmentaite  3 , Kylie R James  3 , Alexander Ross  4 , Delilah Hendriks  1 , Benedetta Artegiani  1 , Georg A Busslinger  1 , Bas Ponsioen  5 , Amanda Andersson-Rolf  1 , Aurelia Saftien  1 , Charelle Boot  1 , Kai Kretzschmar  1 , Maarten H Geurts  1 , Yotam E Bar-Ephraim  1 , Cayetano Pleguezuelos-Manzano  1 , Yorick Post  1 , Harry Begthel  1 , Franka van der Linden  6 , Carmen Lopez-Iglesias  7 , Willine J van de Wetering  8 , Reinier van der Linden  1 , Peter J Peters  7 , Albert J R Heck  2 , Joachim Goedhart  6 , Hugo Snippert  5 , Matthias Zilbauer  9 , Sarah A Teichmann  10 , Wei Wu  2 , Hans Clevers  11
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Free article

High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

Joep Beumer et al. Cell. .
Free article

Erratum in

  • High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells.
    Beumer J, Puschhof J, Bauzá-Martinez J, Martínez-Silgado A, Elmentaite R, James KR, Ross A, Hendriks D, Artegiani B, Busslinger GA, Ponsioen B, Andersson-Rolf A, Saftien A, Boot C, Kretzschmar K, Geurts MH, Bar-Ephraim YE, Pleguezuelos-Manzano C, Post Y, Begthel H, van der Linden F, Lopez-Iglesias C, van de Wetering WJ, van der Linden R, Peters PJ, Heck AJR, Goedhart J, Snippert H, Zilbauer M, Teichmann SA, Wu W, Clevers H. Beumer J, et al. Cell. 2020 Aug 20;182(4):1062-1064. doi: 10.1016/j.cell.2020.08.005. Cell. 2020. PMID: 32822568 No abstract available.

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.

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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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