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

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cam.issuedOnline2018-07-23
dc.contributor.authorBeumer, Joep
dc.contributor.authorArtegiani, Benedetta
dc.contributor.authorPost, Yorick
dc.contributor.authorReimann, Frank
dc.contributor.authorGribble, Fiona
dc.contributor.authorNguyen, Thuc Nghi
dc.contributor.authorZeng, Hongkui
dc.contributor.authorVan den Born, Maaike
dc.contributor.authorVan Es, Johan H
dc.contributor.authorClevers, Hans
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.date.accessioned2018-10-19T10:45:54Z
dc.date.available2018-10-19T10:45:54Z
dc.date.issued2018-07-23
dc.description.abstractEnteroendocrine 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.
dc.identifier.doi10.17863/CAM.31540
dc.identifier.eissn1476-4679
dc.identifier.issn1476-4679
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284173
dc.languageeng
dc.language.isoeng
dc.publisherSpringer Nature
dc.publisher.urlhttps://www.nature.com/articles/s41556-018-0143-y#Sec1
dc.subjectAnimals
dc.subjectBone Morphogenetic Protein 4
dc.subjectCell Differentiation
dc.subjectCell Lineage
dc.subjectCell Movement
dc.subjectEnteroendocrine Cells
dc.subjectGastrointestinal Hormones
dc.subjectHumans
dc.subjectIntestine, Small
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectPhenotype
dc.subjectSignal Transduction
dc.subjectTissue Culture Techniques
dc.titleEnteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient.
dc.typeArticle
dcterms.dateAccepted2018-06-14
prism.endingPage916
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameNature Cell Biology
prism.startingPage909
prism.volume20
pubs.funder-project-idWellcome Trust (106262/Z/14/Z)
pubs.funder-project-idMedical Research Council (MC_UU_12012/5)
pubs.funder-project-idMedical Research Council (MC_UU_12012/3)
pubs.funder-project-idWellcome Trust (084210/Z/07/Z)
pubs.funder-project-idMRC (MC_UU_00014/3)
pubs.funder-project-idMRC (MC_UU_00014/5)
pubs.funder-project-idMedical Research Council (MC_PC_12012)
rioxxterms.licenseref.startdate2018-07-23
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/s41556-018-0143-y

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