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dc.contributor.authorGoolam, Mubeenen
dc.contributor.authorScialdone, Antonioen
dc.contributor.authorGraham, Sarah JLen
dc.contributor.authorMacaulay, Iain Cen
dc.contributor.authorJedrusik, Agnieszkaen
dc.contributor.authorHupalowska, Annaen
dc.contributor.authorVoet, Thierryen
dc.contributor.authorMarioni, Johnen
dc.contributor.authorZernicka-Goetz, Magdalenaen
dc.date.accessioned2016-01-26T15:02:37Z
dc.date.available2016-01-26T15:02:37Z
dc.date.issued2016-03-24en
dc.identifier.citationGoolam et al. Cell (2016) 165: 61-74en
dc.identifier.issn0092-8674
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/253486
dc.description.abstractThe major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterise transcriptomes of all individual cells throughout mouse pre-implantation development. This identifies targets of master pluripotency regulators Oct4 and Sox2 as being highly heterogeneously expressed between blastomeres of the 4-cell embryo, with Sox21 showing one of the most heterogeneous expression profiles. Live-cell tracking demonstrates cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21 results in premature up-regulation of the differentiation regulator Cdx2, suggesting Sox21 helps safeguard pluripotency. Furthermore, Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1, and lowered following CARM1 inhibition, indicating the importance of epigenetic regulation. Therefore, our results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell fate decisions by modulating the balance of pluripotency and differentiation.
dc.description.sponsorshipWe are grateful to the Wellcome Trust, EMBL and CRUK for supporting our work, and our colleagues : M.Shahbazi, D.Glover, F. Antonica for feedback and G. Recher for imaging assistance. Sequence data have been deposited in ArrayExpress (E-MTAB-3321).
dc.languageEnglishen
dc.language.isoenen
dc.publisherCell Press
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.titleHeterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in Four-Cell Mouse Embryosen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.01.047en
prism.endingPage74
prism.publicationDate2016en
prism.publicationNameCellen
prism.startingPage61
prism.volume165en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderCRUK
dcterms.dateAccepted2016-01-22en
rioxxterms.versionofrecord10.1016/j.cell.2016.01.047en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-03-24en
dc.contributor.orcidMarioni, John [0000-0001-9092-0852]
dc.contributor.orcidZernicka-Goetz, Magdalena [0000-0002-7004-2471]
dc.identifier.eissn1097-4172
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEuropean Commission (657995)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales