Cell
Volume 181, Issue 6, 11 June 2020, Pages 1291-1306.e19
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Article
High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

https://doi.org/10.1016/j.cell.2020.04.036Get rights and content
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Highlights

  • A human organoid biobank combines hormone labeling and enteroendocrine cell generation

  • Transcriptomic profiling of human enteroendocrine cells uncovers differences with mice

  • Functional validation of EEC receptors and transcription factors

  • Secretome analysis reveals the repertoire of enteroendocrine secreted products

Summary

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

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

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