A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit

Autor: Chen Gao, Xin Gao, Fei Gao, Xuguang Du, Sen Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-06507-9
Popis: Abstract During early embryonic development, the transition from totipotency to pluripotency is a fundamental and critical process for proper development. However, the regulatory mechanisms governing this transition remain elusive. Here, we conducted a comprehensive genome-wide CRISPR/Cas9 screen to investigate the 2-cell-like cells (2CLCs) phenotype in mouse embryonic stem cells (mESCs). This effort led to the identification of ten regulators that play a pivotal role in determining cell fate during this transition. Notably, our study revealed Mdm2 as a significant negative regulator of 2CLCs, as perturbation of Mdm2 resulted in a higher proportion of 2CLCs. Mdm2 appears to influence cell fate through its impact on cell cycle progression and H3K27me3 epigenetic modifications. In summary, the results of our CRISPR/Cas9 screen have uncovered several genes with distinct functions in regulating totipotency and pluripotency at various levels, offering a valuable resource for potential targets in future molecular studies.
Databáze: Directory of Open Access Journals
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