Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA360135 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:GRHL2-dependent enhancer switching maintains a pluripotent stem cell transcriptional subnetwork after exit from naïve pluripotency
| PRJNA360131 | ENA
Project description:GRHL2-dependent enhancer switching maintains a pluripotent stem cell transcriptional subnetwork after exit from naïve pluripotency [ESC & EpiLC]
| PRJNA448904 | ENA
Project description:GRHL2-dependent enhancer switching maintains a pluripotent stem cell transcriptional subnetwork after exit from naïve pluripotency [ChIP-Seq]
| PRJNA358507 | ENA
Project description:GRHL2-dependent enhancer switching maintains a pluripotent stem cell transcriptional subnetwork after exit from naïve pluripotency [WT & KO]
| PRJNA448903 | ENA
Project description:Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. Genome-wide binding profiles for Foxd3 were investigated in mouse embryonic stem cells (mESC). A mESC line (FH-Foxd3 mESC line) expressing exogenous Foxd3 tagged with Flag and HA epitope (FH-Foxd3) at nearly endogenous levels was generated. ChIPs were performed against FH-Foxd3 using anti-HA or anti-Flag antibodies.
2015-09-14 | E-GEOD-70545 | biostudies-arrayexpress
Project description:At the blastocyst stage, the embryo invades the uterine and the pluripotent epiblast cells get reshaped from an amorphous ball into a polarized cup-shaped epithelium. At the same time, the transiently established naïve pluripotency is dismantled, transforming into a more developmentally advanced post-implantation pluripotent state. The major driver of the differentiation process is the autocrine Fgf/Mek/Erk singling which promotes the exit of naïve pluripotency. However, inhibiting Mek alone is not sufficient to maintain the cells in the naïve state suggesting the contribution of additional, as yet unidentified, pro-differentiation signals. Using a 3D embryonic stem cells (ESC) based model of epiblast development we established an automated pipeline for cell culture and analysis and performed a large-scale functional screen to identify factors regulating the development of the pluripotent lineage. We found that the mitotic kinases – Aurora kinase A (Aurka) and Polo-like kinase (PLK) positively regulate Erk signalling in a Mek-independent manner. We determined that Aurka and Erk form a complex in ESCs and suppression of Aurka activity delays the exit of naïve pluripotency. Moreover, a combination of Aurka and Mek inhibition enabled the de novo derivation of ESC lines from mouse embryos. Interestingly, during cell division, we found that phospho-Erk (pErk) localizes on the spindle poles at prophase and metaphase, gradually decreasing its signal at anaphase and telophase. Proximity biotinylation analysis of the pErk interactome identified the formation of PLK/pErk complex in metaphase cells. Moreover, inhibition of PLK, but not Mek or Aurka, resulted in a substantial decrease in Erk phosphorylation at the mitotic spindle. In summary, our findings demonstrate that the pluripotent cells continuously generate and perceive two types of Erk-mediated pro-differentiation cues - autocrine signals of the Fgf/Mek cascade and cell-intrinsic cues via the mitotic kinase Aurka and PLK. Altogether, these signals promote the exit of naïve pluripotency, driving the transient pace of embryonic development.
2025-11-20 | PXD051298 | Pride
Project description:Following implantation, mouse epiblast cells transit from a naïve to a primed state in which they are competent for both somatic and primordial germ cell (PGC) specification. Using mouse embryonic stem cells (mESC) as an in vitro model to study the transcriptional regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for the exit from naïve pluripotency and the progression to a primed pluripotent state. During this transition, Foxd3 acts as a repressor that dismantles a significant fraction of the naïve pluripotency expression program through the decommissioning of active enhancers associated with key naïve pluripotency and early germline genes. Subsequently, Foxd3 needs to be silenced in primed pluripotent cells to allow the reactivation of relevant genes required for proper PGC specification. Our findings uncover a wave of activation-deactivation of Foxd3 as a crucial step for the exit from naïve pluripotency and subsequent PGC specification. mRNA profiles were generated by RNA-seq in duplicates for each of the following mESC lines: Foxd3fl/fl;Cre-ER mESC maintained in "Serum+LIF" (SL) treated with TM for three days (SL Foxd3-/-); untreated Foxd3fl/fl;Cre-ER SL mESC (SL Foxd3fl/fl); tetON Foxd3 SL mESC treated with Dox for three days; WT SL mESC treated with Dox for three days; Foxd3fl/fl;Cre-ER mESC maintained in "2i+LIF" (2i) treated with TM for three days (2i Foxd3-/-); untreated Foxd3fl/fl;Cre-ER 2i mESC (2i Foxd3fl/fl).
2015-09-14 | E-GEOD-70546 | biostudies-arrayexpress
Project description:It is important to understand how cells can maintain and exit human pluripotency. We exploited the metabolic and epigenetic differences between naïve and primed pluripotent cells to design a CRISPR-Cas9 screen for identifying genes that promote the exit from naïve pluripotency. Among the known and novel regulators of this early step of human development, we identified the tumor suppressor folliculin (FLCN). Flcn is important for implantation of the mouse embryo into the uterus and has been shown to regulate the exit of pluripotency in mouse through activation of Esrrb. However, the function of FLCN is unknown in human embryonic stem cells (hESC). Knock-out (KO) of FLCN revealed that it is not essential to maintain the naïve pluripotent state but is required for the exit of that state, in part by controlling the localization of the transcription factor TFE3. While mainly found in the cytoplasm of cells exiting the naïve state, FLCN KO resulted in TFE3 nuclear localization. TFE3 targets up-regulated in FLCN KO exit assay were members of Wnt pathway and ESRRB. Treatment of FLCN KO hESC with a Wnt inhibitor rescued the phenotype and allowed the cells to exit the naïve state. In contrast, the lack of rescue in ESRRB/FLCN double KO lines suggested that ESRRB was not responsible for the FLCN mutant phenotype. Using co-immunoprecipitation and mass spectrometry analysis we identified unique FLCN binding partners, in addition to known FLCN interactors, at various stages of pluripotency. The interactions of FLCN with components of the mTOR pathway (mTORC1 and mTORC2) revealed a mechanism of FLCN function during exit from naïve pluripotency.
2018-11-03 | GSE122118 | GEO
Project description:The naïve epiblast undergoes a transition to a pluripotent primed state during embryo implantation. Interestingly, a distinct intermediate stage during the naïve-to-primed transition has been recently described, the rosette stage. We propose the transcriptional repressor ERF as the MAPK-dependent switch that controls the exit from the rosette-stage of pluripotency. By using inducible ESC to genetically eliminate all RAS proteins, we show that, while differentiated RasKO ESC are reminiscent of the pluripotent rosette-stage, the absence of ERF overcomes the developmental blockage of RAS-deficient cells from this intermediate state. RNAseq data revealed that deletion of ERF restored the overall gene expression profile to a wild-type level in differentiated RasKO ESC. Mechanistically, ERF ensures naïve pluripotency by strengthening naïve pluripotent transcription factor binding and accessibility at specific ESC enhancers. Moreover, ERF regulates negatively the expression of the DNMT3 de novo methylases, which are essential for the extinction of the naïve transcriptional program. Our data revealed an essential role for ERF in the exit from rosette pluripotency as a regulator of the progression to primed pluripotency.
2021-08-06 | GSE162580 | GEO
Project description:The naïve epiblast undergoes a transition to a pluripotent primed state during embryo implantation. Interestingly, a distinct intermediate stage during the naïve-to-primed transition has been recently described, the rosette stage. We propose the transcriptional repressor ERF as the MAPK-dependent switch that controls the exit from the rosette-stage of pluripotency. By using inducible ESC to genetically eliminate all RAS proteins, we show that, while differentiated RasKO ESC are reminiscent of the pluripotent rosette-stage, the absence of ERF overcomes the developmental blockage of RAS-deficient cells from this intermediate state. RNAseq data revealed that deletion of ERF restored the overall gene expression profile to a wild-type level in differentiated RasKO ESC. Mechanistically, ERF ensures naïve pluripotency by strengthening naïve pluripotent transcription factor binding and accessibility at specific ESC enhancers. Moreover, ERF regulates negatively the expression of the DNMT3 de novo methylases, which are essential for the extinction of the naïve transcriptional program. Our data revealed an essential role for ERF in the exit from rosette pluripotency as a regulator of the progression to primed pluripotency.
2021-08-06 | GSE162579 | GEO