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

Joep Beumer, Benedetta Artegiani, Yorick Post, Frank Reimann, Fiona Gribble, Thuc Nghi Nguyen, Hongkui Zeng, Maaike Van den Born, Johan H Van Es, Hans Clevers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)909-916
Aantal pagina's8
TijdschriftNature Cell Biology
Volume20
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - aug 2018

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