Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272538 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Polycomb Underlies Transcriptional Heterogeneity in Lineage Priming of Embryonic Stem Cells [ChIP-Seq]
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Project description:Polycomb Underlies Transcriptional Heterogeneity in Lineage Priming of Embryonic Stem Cells [ChIP-Seq and GRO-Seq]
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Project description:Polycomb Underlies Transcriptional Heterogeneity in Lineage Priming of Embryonic Stem Cells
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Project description:The cellular microenvironment shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and benefit from hypoxic culture in vitro. Yet, how different components of the hypoxia response impact stem cell transcriptional networks and lineage choices remains unclear. Here we investigated the effect of acute and prolonged hypoxia on stem cell states and differentiation efficiencies of embryonic and extraembryonic cells. We show that prolonged hypoxia enhances differentiation of embryonic stem (ES) cells towards the mesendoderm lineage by transcriptionally priming cells with a primitive streak signature including Wnt3 and T expression. Exposure to hypoxia in ES culture or during formation of gastrulation-mimicking organoids (gastruloids) moderates T expression and enhances structural complexity. Hypoxic gastruloids generated without exogenous Wnt induction can spontaneously elongate and self-organize. Direct gene regulation by Hif1a, combined with DNA demethylation and metabolic rewiring modulate the transcriptional response and phenotypic outcome. Our findings highlight the influence of the microenvironment on stem cell function and provide a rationale supportive of applying physiological conditions in synthetic embryo models.
2022-09-05 | PXD026641 | Pride
Project description:USP7, a ubiquitin-specific peptidase (USP), plays an important role in many cellular processes through its catalytic deubiquitination of various substrates. However, its nuclear function to shape the transcriptional network in mouse embryonic stem cells (mESCs) remains poorly understood. Here, we report that USP7 maintains mESCs identity through both catalytic activity-dependent and -independent repression of lineage differentiation genes. Usp7 depletion attenuates SOX2 level and derepresses lineage differentiation genes thereby compromising mESCs pluripotency. Mechanistically, USP7 deubiquitinates and stabilizes SOX2 to repress mesoendodermal (ME) lineage genes. Moreover, USP7 assembles into RYBP-variant Polycomb repressive complex 1 and contributes to Polycomb chromatin-mediated repression of ME lineage genes in a catalytic activity-dependent manner. Importantly, USP7 deficient in its deubiquitination function is able to maintain RYBP binding to chromatin for repressing primitive endoderm-associated genes. Overall, our study demonstrates that USP7 harbors both catalytic and non-catalytic activity to repress different lineage differentiation genes thereby revealing a previously unrecognized role in controlling gene expression for maintaining mESCs identity.
2023-07-20 | PXD039633 | Pride
Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC12 and PRC21, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. To investigate the link between PRC2 and NuA4, and therefore the the link between H4ac an H3K27me3, we perturbed PRC2 both chemically and genetically.The effects on the histone PTMs were measured with LC-MS/MS.
2025-02-25 | PXD048246 | Pride
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Transcriptional heterogeneity and lineage commitment in myeloid progenitors [ChIP-seq]
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Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC2 and PRC1, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. Interestingly, the EZH2 proxeome included both PRC complexes, while the RNF2 proxeome only identified PRC1 subunits. More than half of the PRC2 proximal proteins are shared with PRC1, revealing the molecular constitution of polycomb chromatin domains. We identified several pluripotency-associated transcription factors, including NANOG, for which we confirmed genomic co-localisation with PRC2. Upon PRC2 disruption, NANOG redistributes to specific sites containing its DNA binding motif. Finally, we compared PRC2 proximal interactomes between naïve mESCs, serum-cultured mESCs and embryoid bodies, altogether providing a comprehensive resource in different cellular contexts that may help to further decipher Polycomb biology.
2025-02-25 | PXD047569 | Pride
Project description:Polycomb Repressive Complexes PRC1 and PRC2 play a crucial role in silencing lineage-specific genes during early embryogenesis. To provide new insights in polycomb biology, we profiled the proximal interactome (proxeome) of the catalytic subunits RNF2 (PRC1) and EZH2 (PRC2) in mouse embryonic stem cells (mESCs). This revealed >100 proteins proximal to PRC2 and PRC1, which mainly comprise transcription factors, transcriptional regulators and RNA binding proteins. Interestingly, the EZH2 proxeome included both PRC complexes, while the RNF2 proxeome only identified PRC1 subunits. More than half of the PRC2 proximal proteins are shared with PRC1, revealing the molecular constitution of polycomb chromatin domains. We identified several pluripotency-associated transcription factors, including NANOG, for which we confirmed genomic co-localisation with PRC2. Upon PRC2 disruption, NANOG redistributes to specific sites containing its DNA binding motif. Finally, we compared PRC2 proximal interactomes between naïve mESCs, serum-cultured mESCs and embryoid bodies, altogether providing a comprehensive resource in different cellular contexts that may help to further decipher Polycomb biology.
2025-02-25 | PXD058327 | Pride