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dc.contributor.authorScognamiglio, Ren
dc.contributor.authorCabezas-Wallscheid, Nen
dc.contributor.authorThier, MCen
dc.contributor.authorAltamura, Sen
dc.contributor.authorReyes, Aen
dc.contributor.authorPrendergast, Áen
dc.contributor.authorBaumgärtner, Den
dc.contributor.authorCarnevalli, LSen
dc.contributor.authorAtzberger, Aen
dc.contributor.authorHaas, Sen
dc.contributor.authorvon Paleske, Len
dc.contributor.authorBoroviak, Thorstenen
dc.contributor.authorWörsdörfer, Pen
dc.contributor.authorEssers, MAen
dc.contributor.authorKloz, Uen
dc.contributor.authorEisenman, RNen
dc.contributor.authorEdenhofer, Fen
dc.contributor.authorBertone, Paulen
dc.contributor.authorHuber, Wen
dc.contributor.authorvan der Hoeven, Fen
dc.contributor.authorSmith, Aen
dc.contributor.authorTrumpp, Aen
dc.date.accessioned2018-02-27T18:49:07Z
dc.date.available2018-02-27T18:49:07Z
dc.date.issued2016-02-11en
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/273603
dc.description.abstractMouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.
dc.description.sponsorshipThis work was supported by the FOR2033 and SFB873 funded by the Deutsche Forschungsgemeinschaft (DFG), the Dietmar Hopp Foundation (all to A.T.), and the Wellcome Trust (to A.S.).
dc.publisherElsevier (Cell Press)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleMyc depletion induces a pluripotent dormant state mimicking diapauseen
dc.typeArticle
prism.endingPage680
prism.issueIdentifier4en
prism.publicationDate2016en
prism.publicationNameCellen
prism.startingPage668
prism.volume164en
dc.identifier.doi10.17863/CAM.20675
dcterms.dateAccepted2015-12-14en
rioxxterms.versionofrecord10.1016/j.cell.2015.12.033en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2016-02-11en
dc.contributor.orcidBertone, Paul [0000-0001-5059-4829]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/M004023/1)


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International