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dc.contributor.authorSozen, Berna
dc.contributor.authorAmadei, Gianluca
dc.contributor.authorCox, Andy
dc.contributor.authorWang, Ran
dc.contributor.authorNa, Ellen
dc.contributor.authorCzukiewska, Sylwia
dc.contributor.authorChappell, Lia
dc.contributor.authorVoet, Thierry
dc.contributor.authorMichel, Geert
dc.contributor.authorJing, Naihe
dc.contributor.authorGlover, David M
dc.contributor.authorZernicka-Goetz, Magdalena
dc.date.accessioned2019-07-17T14:20:54Z
dc.date.available2019-07-17T14:20:54Z
dc.date.issued2018-08
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294716
dc.description.abstractEmbryonic stem cells can be incorporated into the developing embryo and its germ line, but, when cultured alone, their ability to generate embryonic structures is restricted. They can interact with trophoblast stem cells to generate structures that break symmetry and specify mesoderm, but their development is limited as the epithelial-mesenchymal transition of gastrulation cannot occur. Here, we describe a system that allows assembly of mouse embryonic, trophoblast and extra-embryonic endoderm stem cells into structures that acquire the embryo's architecture with all distinct embryonic and extra-embryonic compartments. Strikingly, such embryo-like structures develop to undertake the epithelial-mesenchymal transition, leading to mesoderm and then definitive endoderm specification. Spatial transcriptomic analyses demonstrate that these morphological transformations are underpinned by gene expression patterns characteristic of gastrulating embryos. This demonstrates the remarkable ability of three stem cell types to self-assemble in vitro into gastrulating embryo-like structures undertaking spatio-temporal events of the gastrulating mammalian embryo.
dc.description.sponsorshipEuropean Research Council (669198) Wellcome Trust (098287/Z/12/Z).
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.subjectCell Line
dc.subjectTrophoblasts
dc.subjectEndoderm
dc.subjectAnimals
dc.subjectMice
dc.subjectCoculture Techniques
dc.subjectCell Communication
dc.subjectCell Differentiation
dc.subjectCell Movement
dc.subjectGene Expression Regulation, Developmental
dc.subjectCell Lineage
dc.subjectGestational Age
dc.subjectPhenotype
dc.subjectEmbryo, Mammalian
dc.subjectGastrulation
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectTranscriptome
dc.subjectMouse Embryonic Stem Cells
dc.titleSelf-assembly of embryonic and two extra-embryonic stem cell types into gastrulating embryo-like structures.
dc.typeArticle
prism.endingPage989
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameNat Cell Biol
prism.startingPage979
prism.volume20
dc.identifier.doi10.17863/CAM.41771
dcterms.dateAccepted2018-06-20
rioxxterms.versionofrecord10.1038/s41556-018-0147-7
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidSozen, Berna [0000-0001-5834-5819]
dc.contributor.orcidNa, Ellen [0000-0003-1395-9707]
dc.contributor.orcidZernicka-Goetz, Magdalena [0000-0002-7004-2471]
dc.identifier.eissn1476-4679
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (098287/Z/12/Z)
pubs.funder-project-idEuropean Research Council (669198)
cam.issuedOnline2018-07-23
rioxxterms.freetoread.startdate2019-02-28


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