Genome-wide CRISPR-KO screen uncovers mTORC1-mediated Gsk3 regulation in naive pluripotency maintenance and dissolution
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The genetic basis of naive pluripotency maintenance and loss is a central question in embryonic stem cell biology. Here, we deploy CRISPR-knockout-based screens in mouse embryonic stem cells to interrogate this question through a genome-wide, non-biased approach using the Rex1GFP reporter as a phenotypic readout. This highly sensitive and efficient method identified genes in diverse biological processes and pathways. We uncovered a key role for negative regulators of mTORC1 in maintenance and exit from naive pluripotency and provided an integrated account of how mTORC1 activity influences naive pluripotency through Gsk3. Our study therefore reinforces Gsk3 as the central node and provides a comprehensive, data-rich resource that will improve our understanding of mechanisms regulating pluripotency and stimulate avenues for further mechanistic studies.
Date Issued
2018-07-10
Date Acceptance
2018-06-06
Citation
Cell reports, 2018, 24 (2), pp.489-502
ISSN
2211-1247
Publisher
Elsevier
Start Page
489
End Page
502
Journal / Book Title
Cell reports
Volume
24
Issue
2
Copyright Statement
© 2018 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000438422700021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Cell Biology
COMPLEX
DIFFERENTIATION
EMBRYONIC STEM-CELLS
GAP ACTIVITY
GENETIC SCREENS
GROUND-STATE PLURIPOTENCY
Life Sciences & Biomedicine
MTORC1 PATHWAY
Science & Technology
SELF-RENEWAL
TARGET
TRANSITION
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-07-11