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dc.contributor.authorSurani, A
dc.contributor.authorHackett, Jamie A
dc.contributor.authorHuang, Yun
dc.contributor.authorGunesdogan, Ufuk
dc.contributor.authorHolm-Gretarsson, Kristjan
dc.contributor.authorKobayashi, Toshihiro
dc.date.accessioned2018-09-08T06:34:37Z
dc.date.available2018-09-08T06:34:37Z
dc.date.issued2018-10-16
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279918
dc.description.abstractEarly mammalian development entails transit through naïve pluripotency towards post-implantation epiblast, which subsequently gives rise to primordial germ cells (PGC), the founding germline population. To investigate these cell fate transitions, we developed a compound-reporter to track cellular identity in a model of PGC specification (PGC-like cells;PGCLC), and coupled it with genome-wide CRISPR-screening. We identify key genes both for exit from pluripotency and for acquisition of PGC fate, and characterise a central role for the transcription-regulators Nr5a2 and Zfp296 in germline ontogeny. Abrogation of these genes results in widespread activation (Nr5a2-/-) or inhibition (Zfp296-/-) of WNT-pathway factors in PGCLC. This leads to aberrant upregulation of the somatic programme or failure to activate germline-genes, respectively, and consequently loss of germ cell identity. Our study places Zfp296 and Nr5a2 as key components of an expanded PGC gene regulatory network, and outlines a transferable strategy for identifying critical regulators of complex cell fate decisions.
dc.publisherSpringer Nature
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleTracing the Transitions from Pluripotency to Germ Cell Fate with CRISPR Screening
dc.typeArticle
prism.publicationNameNature Communications
dc.identifier.doi10.17863/CAM.27286
dcterms.dateAccepted2018-08-08
rioxxterms.versionofrecord10.1038/s41467-018-06230-0
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08-08
dc.contributor.orcidSurani, Azim [0000-0002-8640-4318]
dc.contributor.orcidHackett, Jamie [0000-0002-6237-3684]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idCancer Research Uk (None)
cam.issuedOnline2018-10-16
cam.orpheus.successMon Feb 22 07:35:31 GMT 2021 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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