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dc.contributor.authorStirparo, Giuliano Gen
dc.contributor.authorKurowski, Agataen
dc.contributor.authorYanagida, Ayakaen
dc.contributor.authorBates, Lawrenceen
dc.contributor.authorStrawbridge, Stanleyen
dc.contributor.authorHladkou, Siarheien
dc.contributor.authorStuart, Hannah Ten
dc.contributor.authorBoroviak, Thorstenen
dc.contributor.authorRebelo Da Silva, Joseen
dc.contributor.authorNichols, Jenniferen
dc.date.accessioned2021-01-09T00:30:45Z
dc.date.available2021-01-09T00:30:45Z
dc.date.issued2021-01en
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315955
dc.description.abstractOCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 establishes and protects the pluripotent lineage in the embryo, we used comparative single cell transcriptomics and quantitative immunofluorescence on control and OCT4 null blastocyst inner cell masses at two developmental stages. Surprisingly, activation of most pluripotency-associated transcription factors in the early mouse embryo occurs independently of OCT4, with the exception of the JAK/STAT signalling machinery. Concurrently, OCT4 null inner cell masses ectopically activate a subset of trophectoderm-associated genes. Inspection of metabolic pathways implicates regulation of rate-limiting glycolytic enzymes by OCT4, consistent with a role in sustaining glycolysis. Furthermore, upregulation of the lysosomal pathway was specifically detected in OCT4 null embryos. This finding implicates a requirement for OCT4 in production of normal trophectoderm. Collectively, our findings uncover regulation of cellular metabolism and biophysical properties as mechanisms by which OCT4 instructs pluripotency.
dc.description.sponsorshipThis work was supported by the University of Cambridge, BBSRC project grant RG74277, BB/R018588/1 and MR/R017735/1 to HS and LB respectively, MRC PhD studentship for AK and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute.
dc.format.mediumPrinten
dc.languageengen
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectPluripotent Stem Cellsen
dc.subjectAnimalsen
dc.subjectMiceen
dc.subjectSignal Transductionen
dc.subjectGene Expression Regulation, Developmentalen
dc.subjectGlycolysisen
dc.subjectCell Lineageen
dc.subjectEmbryonic Developmenten
dc.subjectSTAT3 Transcription Factoren
dc.subjectOctamer Transcription Factor-3en
dc.subjectBlastocyst Inner Cell Massen
dc.subjectEmbryo, Mammalianen
dc.subjectSingle-Cell Analysisen
dc.titleOCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms.en
dc.typeArticle
prism.issueIdentifier3en
prism.publicationDate2021en
prism.publicationNameProceedings of the National Academy of Sciences of the United States of Americaen
prism.volume118en
dc.identifier.doi10.17863/CAM.63065
dcterms.dateAccepted2020-12-08en
rioxxterms.versionofrecord10.1073/pnas.2008890118en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-01en
dc.contributor.orcidStirparo, Giuliano G [0000-0002-5911-8682]
dc.contributor.orcidKurowski, Agata [0000-0003-0502-571X]
dc.contributor.orcidYanagida, Ayaka [0000-0002-6350-2185]
dc.contributor.orcidBates, Lawrence [0000-0002-2675-309X]
dc.contributor.orcidHladkou, Siarhei [0000-0002-4354-3270]
dc.contributor.orcidSilva, Jose [0000-0001-5487-1117]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/M004023/1)
pubs.funder-project-idWellcome Trust (101861/Z/13/Z)
pubs.funder-project-idMRC (MR/R017735/1)
pubs.funder-project-idBBSRC (BB/R018588/1)
pubs.funder-project-idBBSRC (BB/P003575/1)
cam.orpheus.successMon Jan 25 12:06:04 GMT 2021 - Embargo updated*
rioxxterms.freetoread.startdate2021-07-31


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