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

TY - JOUR

T1 - Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient

AU - Beumer, Joep

AU - Artegiani, Benedetta

AU - Post, Yorick

AU - Reimann, Frank

AU - Gribble, Fiona

AU - Nguyen, Thuc Nghi

AU - Zeng, Hongkui

AU - Van den Born, Maaike

AU - Van Es, Johan H

AU - Clevers, Hans

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41556-018-0143-y

DO - 10.1038/s41556-018-0143-y

M3 - Article

C2 - 30038251

SN - 1465-7392

VL - 20

SP - 909

EP - 916

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -