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dc.contributor.authorBoroviak, Thorsten
dc.contributor.authorChen, Yutong
dc.contributor.authorSiriwardena, Dylan
dc.contributor.authorPavlinek, Adam
dc.contributor.authorPenfold, Christopher A
dc.date.accessioned2022-05-12T23:31:22Z
dc.date.available2022-05-12T23:31:22Z
dc.identifier.issn0950-1991
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337121
dc.description.abstractThe trophoblast lineage safeguards fetal development by mediating embryo implantation, immune-tolerance, nutritional supply and gas exchange. Human trophoblast stem cells (hTSCs) provide a platform to study lineage specification of placental tissues, yet, the regulatory network controlling self-renewal remains elusive. Here, we present a single-cell atlas of human trophoblast development from zygote to mid-gestation together with single-cell profiling of hTSCs. We determine the transcriptional networks of trophoblast lineages in vivo and leverage probabilistic modelling to identify a role for MAPK signalling in trophoblast differentiation. Placenta- and blastoid-derived hTSCs consistently map between late trophectoderm and early cytotrophoblast, in contrast to blastoid-trophoblast, which correspond to trophectoderm. We functionally assess the requirement of the predicted cytotrophoblast network in a siRNA-screen and reveal 15 essential regulators for hTSC self-renewal, including MAZ, NFE2L3, TFAP2C, NR2F2 and CTNNB1. Our human trophoblast atlas provides a powerful analytical resource to delineate trophoblast cell fate acquisition, to elucidate transcription factors required for hTSC self-renewal and to gauge the developmental stage of in vitro cultured cells.
dc.publisherThe Company of Biologists
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleAn integrated atlas of human placental development delineates essential regulators of trophoblast stem cells
dc.typeArticle
dc.date.updated2022-05-12T14:14:01Z
prism.publicationNameDevelopment
dc.identifier.doi10.17863/CAM.84540
dcterms.dateAccepted2022-05-12
rioxxterms.versionAM
dc.identifier.eissn1477-9129
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (206684/Z/17/Z)
pubs.funder-project-idRoyal Society (IEC\R3\183044)
cam.orpheus.counter5*
cam.depositDate2022-05-12
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2025-05-12


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