Tracing the Transitions from Pluripotency to Germ Cell Fate with CRISPR Screening
dc.contributor.author | Surani, Azim | |
dc.contributor.author | Hackett, Jamie | |
dc.contributor.author | Huang, Yun | |
dc.contributor.author | Gunesdogan, Ufuk | |
dc.contributor.author | Holm-Gretarsson, Kristjan | |
dc.contributor.author | Kobayashi, Toshihiro | |
dc.date.accessioned | 2018-09-08T06:34:37Z | |
dc.date.available | 2018-09-08T06:34:37Z | |
dc.date.issued | 2018-10-16 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/279918 | |
dc.description.abstract | Early 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.publisher | Springer Nature | |
dc.rights | Attribution 4.0 International (CC BY) | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Tracing the Transitions from Pluripotency to Germ Cell Fate with CRISPR Screening | |
dc.type | Article | |
prism.publicationName | Nature Communications | |
dc.identifier.doi | 10.17863/CAM.27286 | |
dcterms.dateAccepted | 2018-08-08 | |
rioxxterms.versionofrecord | 10.1038/s41467-018-06230-0 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-08-08 | |
dc.contributor.orcid | Surani, Azim [0000-0002-8640-4318] | |
dc.contributor.orcid | Hackett, Jamie [0000-0002-6237-3684] | |
dc.identifier.eissn | 2041-1723 | |
rioxxterms.type | Journal Article/Review | |
pubs.funder-project-id | Wellcome Trust (092096/Z/10/Z) | |
pubs.funder-project-id | Cancer Research Uk (None) | |
cam.issuedOnline | 2018-10-16 | |
cam.orpheus.success | Mon Feb 22 07:35:31 GMT 2021 - The item has an open VoR version. | |
rioxxterms.freetoread.startdate | 2100-01-01 |
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