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dc.contributor.authorStirparo, Giuliano G
dc.contributor.authorKurowski, Agata
dc.contributor.authorYanagida, Ayaka
dc.contributor.authorBates, Lawrence E
dc.contributor.authorStrawbridge, Stanley E
dc.contributor.authorHladkou, Siarhei
dc.contributor.authorStuart, Hannah T
dc.contributor.authorBoroviak, Thorsten E
dc.contributor.authorSilva, Jose CR
dc.contributor.authorNichols, Jennifer
dc.date.accessioned2021-01-09T00:30:45Z
dc.date.available2021-01-09T00:30:45Z
dc.date.issued2021-01-19
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 signaling machinery. Concurrently, OCT4 null inner cell masses ectopically activate a subset of trophectoderm-associated genes. Inspection of metabolic pathways implicates the regulation of rate-limiting glycolytic enzymes by OCT4, consistent with a role in sustaining glycolysis. Furthermore, up-regulation of the lysosomal pathway was specifically detected in OCT4 null embryos. This finding implicates a requirement for OCT4 in the 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.mediumPrint
dc.languageeng
dc.publisherProceedings of the National Academy of Sciences
dc.rightsAll rights reserved
dc.subjectPluripotent Stem Cells
dc.subjectAnimals
dc.subjectMice
dc.subjectSignal Transduction
dc.subjectGene Expression Regulation, Developmental
dc.subjectGlycolysis
dc.subjectCell Lineage
dc.subjectEmbryonic Development
dc.subjectSTAT3 Transcription Factor
dc.subjectOctamer Transcription Factor-3
dc.subjectBlastocyst Inner Cell Mass
dc.subjectEmbryo, Mammalian
dc.subjectSingle-Cell Analysis
dc.titleOCT4 induces embryonic pluripotency via STAT3 signaling and metabolic mechanisms.
dc.typeArticle
prism.issueIdentifier3
prism.publicationDate2021
prism.publicationNameProc Natl Acad Sci U S A
prism.volume118
dc.identifier.doi10.17863/CAM.63065
dcterms.dateAccepted2020-12-08
rioxxterms.versionofrecord10.1073/pnas.2008890118
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-01
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 E [0000-0002-2675-309X]
dc.contributor.orcidHladkou, Siarhei [0000-0002-4354-3270]
dc.contributor.orcidSilva, Jose CR [0000-0001-5487-1117]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Review
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/M004023/1)
pubs.funder-project-idWellcome Trust (101861/Z/13/Z)
pubs.funder-project-idMedical Research Council (MR/R017735/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/R018588/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P003575/1)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2021-01-15
cam.orpheus.successMon Jan 25 12:06:04 GMT 2021 - Embargo updated
rioxxterms.freetoread.startdate2021-07-31


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