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

文献类型： 外文期刊

第一作者： Gao, Chen

作者： Gao, Chen;Gao, Xin;Gao, Fei;Du, Xuguang;Wu, Sen;Gao, Chen;Gao, Xin;Gao, Fei;Du, Xuguang;Wu, Sen

作者机构：

期刊名称：COMMUNICATIONS BIOLOGY （ 影响因子：5.2； 五年影响因子：5.6 ）

ISSN：

年卷期： 2024 年 7 卷 1 期

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收录情况： SCI

摘要： 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.

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