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16.10.18 CRISPR screen identifies further genes that regulate mouse germ cell specification

last modified Oct 17, 2018 08:03 PM
A team of current and former Surani lab researchers apply fluorescent reporters with a genome-wide CRISPR screen to track changing cellular identity in a model of developing primordial germ cells
16.10.18 CRISPR screen identifies further genes that regulate mouse germ cell specification

Fig 1c (extract): FACS analysis of reporter activation during in vitro cell fate transitions to PGCLCs

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

Hackett JA et al. (2018) Nature Communications Vol 9: 4292.

DOI: 10.1038/s41467-018-06230-0

 

Abstract from the paper

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.

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Read more about research in the Surani lab

Watch Azim Surani describe his early work on genomic imprinting in this video

Studying development to understand disease

The Gurdon Institute is funded by Wellcome and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.

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