Tracing the transitions from pluripotency to germ cell fate with CRISPR screening View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Jamie A Hackett, Yun Huang, Ufuk Günesdogan, Kristjan A Gretarsson, Toshihiro Kobayashi, M Azim Surani

ABSTRACT

Early mammalian development entails transit through naive 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. More... »

PAGES

4292

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-06230-0

DOI

http://dx.doi.org/10.1038/s41467-018-06230-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107542092

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30327475


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283 https://www.grid.ac/institutes/grid.467811.d schema:alternateName National Institute for Physiological Sciences
284 schema:name Center for Genetic Analysis of Behaviour, National Institute for Physiological Sciences, 5-1 Higashiyama Myodaiji, Okazaki, Aichi, 444-8787, Japan.
285 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
286 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
287 rdf:type schema:Organization
288 https://www.grid.ac/institutes/grid.5335.0 schema:alternateName University of Cambridge
289 schema:name Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
290 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. a.surani@gurdon.cam.ac.uk.
291 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. jamie.hackett@embl.it.
292 Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), via Ramarini 32, 00015, Rome, Italy. jamie.hackett@embl.it.
293 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
294 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK. a.surani@gurdon.cam.ac.uk.
295 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK. jamie.hackett@embl.it.
296 rdf:type schema:Organization
297 https://www.grid.ac/institutes/grid.7450.6 schema:alternateName University of Göttingen
298 schema:name Department of Developmental Biology, University of Göttingen, Göttingen Center for Molecular Biosciences, Justus-von-Liebig Weg 11, 37077, Göttingen, Germany.
299 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK.
300 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
301 rdf:type schema:Organization
 




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