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dc.contributor.authorCollier, Amanda J
dc.contributor.authorBendall, Adam
dc.contributor.authorFabian, Charlene
dc.contributor.authorMalcolm, Andrew
dc.contributor.authorTilgner, Katarzyna
dc.contributor.authorSemprich, Claudia I
dc.contributor.authorWojdyla, Katarzyna
dc.contributor.authorNisi, Paola Serena
dc.contributor.authorKishore, Kamal
dc.contributor.authorRoamio Franklin, Valar Nila
dc.contributor.authorMirshekar-Syahkal, Bahar
dc.contributor.authorD'Santos, Clive
dc.contributor.authorPlath, Kathrin
dc.contributor.authorYusa, Kosuke
dc.contributor.authorRugg-Gunn, Peter J
dc.date.accessioned2022-04-26T01:02:40Z
dc.date.available2022-04-26T01:02:40Z
dc.date.issued2022-03-25
dc.identifier.issn2375-2548
dc.identifier.other35333572
dc.identifier.otherPMC8956265
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336442
dc.description.abstractUncovering the mechanisms that establish naïve pluripotency in humans is crucial for the future applications of pluripotent stem cells including the production of human blastoids. However, the regulatory pathways that control the establishment of naïve pluripotency by reprogramming are largely unknown. Here, we use genome-wide screening to identify essential regulators as well as major impediments of human primed to naïve pluripotent stem cell reprogramming. We discover that factors essential for cell state change do not typically undergo changes at the level of gene expression but rather are repurposed with new functions. Mechanistically, we establish that the variant Polycomb complex PRC1.3 and PRDM14 jointly repress developmental and gene regulatory factors to ensure naïve cell reprogramming. In addition, small-molecule inhibitors of reprogramming impediments improve naïve cell reprogramming beyond current methods. Collectively, this work defines the principles controlling the establishment of human naïve pluripotency and also provides new insights into mechanisms that destabilize and reconfigure cell identity during cell state transitions.
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101653440
dc.sourceessn: 2375-2548
dc.subjectPluripotent Stem Cells
dc.subjectHumans
dc.subjectCell Differentiation
dc.subjectGene Expression Regulation
dc.subjectPolycomb Repressive Complex 1
dc.subjectCellular Reprogramming
dc.titleGenome-wide screening identifies Polycomb repressive complex 1.3 as an essential regulator of human naïve pluripotent cell reprogramming.
dc.typeArticle
dc.date.updated2022-04-26T01:02:40Z
prism.issueIdentifier12
prism.publicationNameSci Adv
prism.volume8
dc.identifier.doi10.17863/CAM.83859
dcterms.dateAccepted2022-02-02
rioxxterms.versionofrecord10.1126/sciadv.abk0013
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCollier, Amanda J [0000-0003-1137-6874]
dc.contributor.orcidBendall, Adam [0000-0002-6865-2625]
dc.contributor.orcidMalcolm, Andrew [0000-0001-6240-7701]
dc.contributor.orcidSemprich, Claudia I [0000-0002-2446-9028]
dc.contributor.orcidWojdyla, Katarzyna [0000-0003-4509-1818]
dc.contributor.orcidKishore, Kamal [0000-0002-4650-8745]
dc.contributor.orcidMirshekar-Syahkal, Bahar [0000-0002-2337-9442]
dc.contributor.orcidD'Santos, Clive [0000-0003-3425-7288]
dc.contributor.orcidPlath, Kathrin [0000-0001-7796-3372]
dc.contributor.orcidYusa, Kosuke [0000-0002-3442-021X]
dc.contributor.orcidRugg-Gunn, Peter J [0000-0002-9601-5949]
dc.identifier.eissn2375-2548
pubs.funder-project-idNICHD NIH HHS (R01 HD098387)
pubs.funder-project-idWellcome Trust (206194)
pubs.funder-project-idNIGMS NIH HHS (P01 GM099134)
cam.issuedOnline2022-03-25


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