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

Accepted version
Peer-reviewed

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Authors

Beumer, Joep 
Artegiani, Benedetta 
Post, Yorick 

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.

Description

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

Conference Name

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)
Medical Research Council (MC_PC_12012)