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dc.contributor.authorArgelaguet, Ricardoen
dc.contributor.authorClark, Stephen Jamesen
dc.contributor.authorMohammed, Hishamen
dc.contributor.authorStapel, Lisa Carineen
dc.contributor.authorKrueger, Christelen
dc.contributor.authorKapourani, Chantriolnt-Andreasen
dc.contributor.authorImaz-Rosshandler, Ivanen
dc.contributor.authorLohoff, Timen
dc.contributor.authorXiang, Yunlongen
dc.contributor.authorHanna, Courtneyen
dc.contributor.authorSmallwood, Sebastienen
dc.contributor.authorIbarra-Soria, Ximenaen
dc.contributor.authorBuettner, Florianen
dc.contributor.authorSanguinetti, Guidoen
dc.contributor.authorXie, Weien
dc.contributor.authorKrueger, Felixen
dc.contributor.authorGottgens, Bertholden
dc.contributor.authorRugg-Gunn, Peter Jen
dc.contributor.authorKelsey, Gavinen
dc.contributor.authorDean, Wendyen
dc.contributor.authorNichols, Jenniferen
dc.contributor.authorStegle, Oliveren
dc.contributor.authorMarioni, John Cen
dc.contributor.authorReik, Wolfen
dc.date.accessioned2019-10-30T00:31:05Z
dc.date.available2019-10-30T00:31:05Z
dc.date.issued2019-12-11en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/298216
dc.description.abstractFormation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan and is associated with major transcriptional changes. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell fate choice remains unresolved, and the coordination between different molecular layers is unclear. Here we describe the first single cell triple-omics map of chromatin accessibility, DNA methylation and RNA expression during the onset of gastrulation in mouse embryos. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements at enhancer marks, driven by TET-mediated demethylation, and a concomitant increase of accessibility. In striking contrast, the methylation and accessibility landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or remodelled prior to cell fate decisions, providing the molecular logic for a hierarchical emergence of the primary germ layers.
dc.description.sponsorshipCRUK, Wellcome Trust, MRC, BBSRC, EMBL, EU
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectChromatinen
dc.subjectPluripotent Stem Cellsen
dc.subjectGastrulaen
dc.subjectEndodermen
dc.subjectMesodermen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectRNAen
dc.subjectFactor Analysis, Statisticalen
dc.subjectCell Differentiationen
dc.subjectErythropoiesisen
dc.subjectDNA Methylationen
dc.subjectEpigenesis, Geneticen
dc.subjectGene Expression Regulation, Developmentalen
dc.subjectZinc Fingersen
dc.subjectCell Lineageen
dc.subjectTime Factorsen
dc.subjectGastrulationen
dc.subjectEnhancer Elements, Geneticen
dc.subjectEmbryoid Bodiesen
dc.subjectSingle-Cell Analysisen
dc.subjectDemethylationen
dc.subjectEpigenomeen
dc.titleMulti-omics profiling of mouse gastrulation at single-cell resolution.en
dc.typeArticle
prism.endingPage491
prism.issueIdentifier7787en
prism.publicationDate2019en
prism.publicationNameNatureen
prism.startingPage487
prism.volume576en
dc.identifier.doi10.17863/CAM.45268
dcterms.dateAccepted2019-10-22en
rioxxterms.versionofrecord10.1038/s41586-019-1825-8en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-12-11en
dc.contributor.orcidArgelaguet, Ricardo [0000-0003-3199-3722]
dc.contributor.orcidClark, Stephen James [0000-0002-6183-491X]
dc.contributor.orcidStapel, Lisa Carine [0000-0003-0808-5005]
dc.contributor.orcidKapourani, Chantriolnt-Andreas [0000-0003-2303-1953]
dc.contributor.orcidImaz-Rosshandler, Ivan [0000-0001-5975-0138]
dc.contributor.orcidLohoff, Tim [0000-0001-9333-842X]
dc.contributor.orcidHanna, Courtney [0000-0002-4063-5575]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.contributor.orcidStegle, Oliver [0000-0002-8818-7193]
dc.contributor.orcidReik, Wolf [0000-0003-0216-9881]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (105031/D/14/Z)
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idWellcome Trust (108438/E/15/Z)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idBBSRC (BB/M004023/1)
pubs.funder-project-idBBSRC (BB/S001816/1)
cam.orpheus.successThu Jan 30 10:36:24 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-06-11


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