Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient

Nat Cell Biol. 2018 Aug;20(8):909-916. doi: 10.1038/s41556-018-0143-y. Epub 2018 Jul 23.

Abstract

Enteroendocrine cells (EECs) control a wide range of physiological processes linked to metabolism1. We show that EEC hormones are differentially expressed between crypts (for example, Glp1) and villi (for example, secretin). As demonstrated by single-cell mRNA sequencing using murine Lgr5+ cell-derived organoids, BMP4 signals alter the hormone expression profiles of individual EECs to resemble those found in the villus. Accordingly, BMP4 induces hormone switching of EECs migrating up the crypt-villus axis in vivo. Our findings imply that EEC lineages in the small intestine exhibit a more flexible hormone repertoire than previously proposed. We also describe a protocol to generate human EECs in organoids and demonstrate a similar regulation of hormone expression by BMP signalling. These findings establish alternative strategies to target EECs with therapeutically relevant hormone production through BMP modulation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4 / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Lineage*
  • Cell Movement / drug effects*
  • Enteroendocrine Cells / metabolism*
  • Gastrointestinal Hormones / metabolism*
  • Humans
  • Intestine, Small / cytology
  • Intestine, Small / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Signal Transduction / drug effects*
  • Tissue Culture Techniques

Substances

  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Gastrointestinal Hormones