High-Resolution mRNA and Secretome Atlas of Human Enteroendocrine Cells

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Enteroendocrine Cells / metabolism*
  • Gastrointestinal Hormones / genetics
  • Gastrointestinal Tract / metabolism
  • Glucagon-Like Peptide 1 / genetics
  • Humans
  • Organoids / metabolism
  • RNA, Messenger / genetics*
  • Transcription Factors / genetics
  • Transcriptome / genetics


  • Gastrointestinal Hormones
  • RNA, Messenger
  • Transcription Factors
  • Glucagon-Like Peptide 1