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EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-seq]

ABSTRACT: EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-seq]

PROVIDER: PRJNA1047637 | ENA |

REPOSITORIES: ENA

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EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

Project description:Pluripotent stem cell identities such as differentiation and infinite proliferation have long been decoded in the frameworks of transcription factor networks, epigenomes, and signal transduction, yet unclear and fragmented. However, directing attention toward translation regulation, the bridge between these events promises to provide new insights into previously unexplained mechanisms. Functional screening led to the discovery that EIF3D maintains primed pluripotency via selective translation regulation. The loss of EIF3D unbalanced the pluripotency-associated signaling pathways, disrupting primed pluripotency. Furthermore, we found that EIF3D safeguards robust proliferation by managing the translation of multiple p53 regulators that maintain low p53 activity in the undifferentiated state. Therefore, this study provides a paradigm for selective translation regulation that defines the primed pluripotent stem cell identity.

2025-04-10 | GSE248819 | GEO

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [Ribo-seq]

2025-04-10 | GSE249191 | GEO

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-seq]

2025-04-10 | GSE249190 | GEO

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-Seq]

2025-04-10 | GSE248702 | GEO

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

Project description:EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

| PRJNA1046063 | ENA

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

Project description:EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

| PRJNA1046058 | ENA

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-Seq]

Project description:EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [RNA-Seq]

| PRJNA1045619 | ENA

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [Ribo-seq]

Project description:EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency [Ribo-seq]

| PRJNA1047636 | ENA

EIF3D Safeguards the Homeostasis of Key Signaling Pathways in Human Primed Pluripotency

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-04-10 | GSE248820 | GEO

The translational landscape of naïve and primed state pluripotency

Project description:Translational control plays a central role in regulation of gene expression and can lead to significant divergence between mRNA- and protein-abundance. The translational landscape of early mammalian development and its impact on cellular proteome, however, remains largely un-explored. Here we used genome-wide approaches combined with time-course analysis to measure the mRNA-abundance, mRNA-translation rate and protein expression during the transition of naïve into primed embryonic stem cells (ESCs). We found that the ground state ESCs cultured with GSK3- and MEK-inhibitors and LIF (2iL) display higher ribosome density on a selective set of mRNAs. These mRNAs show reduced translation during the exit from ground state pluripotency and transition to serum/LIF (SL) culture or upon commitment to primed epiblast-like stem cells (EpiLSCs). Strikingly, integrative analysis with cellular proteome indicate a strong translational buffering of this set of mRNAs in 2iL-ESCs leading to stable protein expression levels. Our data reveal that the global alteration of cellular proteome is largely accompanied by transcriptional rewiring. Furthermore, we identified a set of genes (including UHRF1 and KRAS) that undergo selective post-translational regulation during the transition of naïve into primed pluripotency and linked the observed changes to upstream GSK- and MEK/MAPK-signaling pathways using single inhibitor treated ESCs. Thus, we provide a comprehensive and detailed overview of the global changes in gene expression during the transition of naïve to primed pluripotency and dissect the relative contributions of RNA-transcription, translation and regulation of protein stability in controlling protein abundance.

2020-04-03 | PXD014528 | Pride

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