Synapse - Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness

Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness Journal Article

Authors:	Rosen, B. P.; Li, Q. V.; Cho, H. S.; Liu, D.; Yang, D.; Graff, S.; Yan, J.; Luo, R.; Verma, N.; Damodaran, J. R.; Kale, H. T.; Kaplan, S. J.; Beer, M. A.; Sidoli, S.; Huangfu, D.
Article Title:	Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness
Abstract:	Pluripotent stem cells have remarkable self-renewal capacity: the ability to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into almost any cell type in the body. To investigate the interplay between these two aspects of self-renewal, we perform four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSCs and the dissolution of primed pluripotent identity during early differentiation. These screens distinguish genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation. We further identify a core set of genes controlling both stem cell fitness and pluripotent identity, including a network of chromatin factors. Here, unbiased screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide a valuable resource for exploring pluripotent stem cell identity versus cell fitness, and offer a framework for categorizing gene function. © The Author(s) 2024.
Keywords:	genetics; cytology; metabolism; cell differentiation; chromatin; human genome; pluripotent stem cell; pluripotent stem cells; genome, human; cell self-renewal; cell self renewal; humans; human; crispr cas system; crispr-cas systems
Journal Title:	Nature Communications
Volume:	15
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2024-10-17
Start Page:	8966
Language:	English
DOI:	10.1038/s41467-024-53284-4
PUBMED:	39419994
PROVIDER:	scopus
PMCID:	PMC11487130
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85206796421&doi=10.1038%2fs41467-024-53284-4&partnerID=40&md5=de9ee3574646b53e98e403c0f7f24426
Notes:	Article -- Source: Scopus