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A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [RNA-Seq]

ABSTRACT: A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [RNA-Seq]

PROVIDER: PRJNA1120448 | ENA |

REPOSITORIES: ENA

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A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [CUT&Tag]

Project description: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. In this study, 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.

2024-07-01 | GSE269169 | GEO

A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [RNA-Seq]

2024-07-01 | GSE269168 | GEO

A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [CUT&Tag]

Project description:A CRISPR/Cas9 screen in embryonic stem cells reveals that Mdm2 regulates totipotency exit [CUT&Tag]

| PRJNA1120447 | ENA

The homeobox transcription factor DUXBL controls exit from totipotency

Project description:The homeobox transcription factor DUXBL controls exit from totipotency

| PRJNA979244 | ENA

CRISPR-Cas9 RBM10 synthetic lethality screen

Project description:Genome-wide CRISPR-Cas9 knockout screen using TKOv1 sgRNA library was performed in isogenic RBM10-proficient and RBM10-deficient HCC827 cells.

2023-03-04 | E-MTAB-12724 | biostudies-arrayexpress

The homeobox transcription factor DUXBL controls exit from totipotency

Project description:In mice, exit from the totipotent 2-cell (2C) embryo stage requires silencing of the 2C-associated transcriptional program. However, the molecular mechanisms involved in this process remain poorly understood. Here, we demonstrate that the 2C-specific transcription factor DUX mediates an essential negative feedback loop by inducing the expression of DUXBL to promote this silencing.We show that DUXBL gains accessibility to DUX-bound regions specifically upon DUX expression.Furthermore, we determine that DUXBL interacts with TRIM24 and TRIM33, members of the tripartite motif superfamily involved in gene silencing and co-localizes with them in nuclear foci upon DUX expression. Importantly, DUXBL overexpression impairs 2C-associated transcription, whereas Duxbl inactivation in ESC increases DUX-dependent induction of the 2C-transcriptional program. Consequently, DUXBL deficiency in embryos results in sustained expression of 2C-associated transcripts, leading to early developmental arrest.Our study identifies DUXBL as an essential regulator of totipotency exit enabling the first divergence of cell fates.

2023-12-07 | GSE234053 | GEO

CRISPR-Cas9 RBM10 synthetic lethality screen

Project description:CRISPR-Cas9 RBM10 synthetic lethality screen

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Genome-wide CRISPR-Cas9 screen in isogenic parental and RBM10-KO HCC827 cells

Project description:Genome-wide CRISPR-Cas9 knockout screen using TKOv1 sgRNA library performed in isogenic RBM10-proficient and RBM10-deficient HCC827 cells.

2024-03-01 | E-MTAB-13626 | biostudies-arrayexpress

OCI-AML5-Cas9 EKO chemogenomic CRISPR screen

Project description:OCI-AML5-Cas9 EKO chemogenomic CRISPR screen

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OCI-AML1-Cas9 EKO chemogenomic CRISPR screen

Project description:OCI-AML1-Cas9 EKO chemogenomic CRISPR screen

| PRJNA660782 | ENA