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

Authors
Beumer, Joep 
Artegiani, Benedetta 
Post, Yorick 

Change log
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 Date
2018-07-23
Online Publication Date
2018-07-23
Acceptance Date
2018-06-14
Keywords
Animals, Bone Morphogenetic Protein 4, Cell Differentiation, Cell Lineage, Cell Movement, Enteroendocrine Cells, Gastrointestinal Hormones, Humans, Intestine, Small, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Signal Transduction, Tissue Culture Techniques
Journal Title
Nature Cell Biology
Journal ISSN
1476-4679
1476-4679
Volume Title
20
Publisher
Springer Nature
Sponsorship
Wellcome Trust (106262/Z/14/Z)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_UU_12012/3)
Wellcome Trust (084210/Z/07/Z)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)