High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

45 Citations (Web of Science)
33 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1291-+
Number of pages35
JournalCell
Volume181
Issue number6
DOIs
Publication statusPublished - 11 Jun 2020

Keywords

  • GLUCAGON-LIKE PEPTIDE-1
  • SMALL-INTESTINE
  • CHROMOGRANIN-A
  • STEM-CELLS
  • GENE
  • RECEPTOR
  • PROTEIN
  • SEROTONIN
  • DIFFERENTIATION
  • EXPRESSION

Cite this