Similar Datasets
Project description:The organization of chromatin, governed by physicochemical interactions, nucleosome positioning, and histone modifications, regulates transcription to influence cellular plasticity and cell fate. We explored whether the organization of chromatin into nanoscale packing domains is involved in regulating transcriptional programs that govern stemness and responses to chemotherapy. Specifically, chromatin packing domains are a unit of chromatin structure at the single-cell level playing a critical role in regulating cellular transcriptional plasticity and access to the transcriptional landscape. Using an optical spectroscopic nanosensing technology, partial wave spectroscopic (PWS) microscopy, we show that ovarian cancer-derived cancer stem cells (CSCs) display upregulation of nanoscale chromatin packing domains (P<0.05) compared to non-CSCs cells. CUT&Tag sequencing with antibodies for repressive H3K27me3 and active H3K4me3 and H3K27ac marks identified 4438 H3K27me3 differentially enriched regions (P<0.05), of which 2786 were detected in CSCs, supporting chromatin packing domain upregulation in ovarian CSCs. Additionally, more poised genes with both H3K4me3 and H3K27me3 marks were identified in CSCs (n=2292) vs. non-CSCs (n=932), supporting the increased transcriptional plasticity of CSCs. Corresponding to the distinct organization of chromatin marks in CSCs, comparative transcriptomic analyses yielded a higher intercellular transcriptional heterogeneity in global gene expression at baseline in CSCs vs. non-CSCs. In response to cisplatin, genes with low baseline expression levels underwent the highest upregulation in CSCs, demonstrating transcriptional plasticity under the stress of chemotherapy. Treatment of CSCs with epigenome targeting drugs downregulating chromatin packing domain formation promoted cellular differentiation. In particular, the Dot1L inhibitor (Dot1Li) downregulated chromatin domains and blocked transcriptional plasticity. This resulted in the reversal of stemness features and inhibition of tumor initiation capacity. The results support that CSCs harbor upregulated chromatin packing domains, contributing to transcriptional and cell plasticity that epigenome modifiers can target.
2025-03-18 | GSE268060 | GEO
Project description:The organization of chromatin, governed by physicochemical interactions, nucleosome positioning, and histone modifications, regulates transcription to influence cellular plasticity and cell fate. We explored whether the organization of chromatin into nanoscale packing domains is involved in regulating transcriptional programs that govern stemness and responses to chemotherapy. Specifically, chromatin packing domains are a unit of chromatin structure at the single-cell level playing a critical role in regulating cellular transcriptional plasticity and access to the transcriptional landscape. Using an optical spectroscopic nanosensing technology, partial wave spectroscopic (PWS) microscopy, we show that ovarian cancer-derived cancer stem cells (CSCs) display upregulation of nanoscale chromatin packing domains (P<0.05) compared to non-CSCs cells. CUT&Tag sequencing with antibodies for repressive H3K27me3 and active H3K4me3 and H3K27ac marks identified 4438 H3K27me3 differentially enriched regions (P<0.05), of which 2786 were detected in CSCs, supporting chromatin packing domain upregulation in ovarian CSCs. Additionally, more poised genes with both H3K4me3 and H3K27me3 marks were identified in CSCs (n=2292) vs. non-CSCs (n=932), supporting the increased transcriptional plasticity of CSCs. Corresponding to the distinct organization of chromatin marks in CSCs, comparative transcriptomic analyses yielded a higher intercellular transcriptional heterogeneity in global gene expression at baseline in CSCs vs. non-CSCs. In response to cisplatin, genes with low baseline expression levels underwent the highest upregulation in CSCs, demonstrating transcriptional plasticity under the stress of chemotherapy. Treatment of CSCs with epigenome targeting drugs downregulating chromatin packing domain formation promoted cellular differentiation. In particular, the Dot1L inhibitor (Dot1Li) downregulated chromatin domains and blocked transcriptional plasticity. This resulted in the reversal of stemness features and inhibition of tumor initiation capacity. The results support that CSCs harbor upregulated chromatin packing domains, contributing to transcriptional and cell plasticity that epigenome modifiers can target.
2025-03-18 | GSE268062 | GEO
Project description:The organization of chromatin, governed by physicochemical interactions, nucleosome positioning, and histone modifications, regulates transcription to influence cellular plasticity and cell fate. We explored whether the organization of chromatin into nanoscale packing domains is involved in regulating transcriptional programs that govern stemness and responses to chemotherapy. Specifically, chromatin packing domains are a unit of chromatin structure at the single-cell level playing a critical role in regulating cellular transcriptional plasticity and access to the transcriptional landscape. Using an optical spectroscopic nanosensing technology, partial wave spectroscopic (PWS) microscopy, we show that ovarian cancer-derived cancer stem cells (CSCs) display upregulation of nanoscale chromatin packing domains (P<0.05) compared to non-CSCs cells. CUT&Tag sequencing with antibodies for repressive H3K27me3 and active H3K4me3 and H3K27ac marks identified 4438 H3K27me3 differentially enriched regions (P<0.05), of which 2786 were detected in CSCs, supporting chromatin packing domain upregulation in ovarian CSCs. Additionally, more poised genes with both H3K4me3 and H3K27me3 marks were identified in CSCs (n=2292) vs. non-CSCs (n=932), supporting the increased transcriptional plasticity of CSCs. Corresponding to the distinct organization of chromatin marks in CSCs, comparative transcriptomic analyses yielded a higher intercellular transcriptional heterogeneity in global gene expression at baseline in CSCs vs. non-CSCs. In response to cisplatin, genes with low baseline expression levels underwent the highest upregulation in CSCs, demonstrating transcriptional plasticity under the stress of chemotherapy. Treatment of CSCs with epigenome targeting drugs downregulating chromatin packing domain formation promoted cellular differentiation. In particular, the Dot1L inhibitor (Dot1Li) downregulated chromatin domains and blocked transcriptional plasticity. This resulted in the reversal of stemness features and inhibition of tumor initiation capacity. The results support that CSCs harbor upregulated chromatin packing domains, contributing to transcriptional and cell plasticity that epigenome modifiers can target.
2025-03-18 | GSE268061 | GEO
Project description:Chromatin Organization Governs Transcriptional Response and Plasticity of Cancer Stem Cells
| PRJNA1114787 | ENA
Project description:Chromatin Organization Governs Transcriptional Response and Plasticity of Cancer Stem Cells [RNA]
| PRJNA1114111 | ENA
Project description:Chromatin Organization Governs Transcriptional Response and Plasticity of Cancer Stem Cells [scRNA-seq]
| PRJNA1114115 | ENA
Project description:Chromatin Organization Governs Transcriptional Response and Plasticity of Cancer Stem Cells [CUT&Tag]
| PRJNA1114116 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-17 | GSE235947 | GEO
Project description:Hypoxia has been long-time acknowledged as major cancer-promoting microenvironment. In such an energy-restrictive condition, post-transcriptional mechanisms gain importance over the energy-expensive gene transcription machinery. Here we show that the onset of hypoxia-induced cancer stem cell features requires the beta-catenin-dependent post-transcriptional up-regulation of CA9 and SNAI2 gene expression. In response to hypoxia, beta-catenin moves from the plasma membrane to the cytoplasm where it binds and stabilizes SNAI2 and CA9 mRNAs, in cooperation with the mRNA stabilizing protein HuR. We also provide evidence that the post-transcriptional activity of cytoplasmic beta-catenin operates under normoxia in basal-like/triple-negative breast cancer cells, where the beta-catenin knockdown suppresses the stem cell phenotype in vitro and tumor growth in vivo. In such cells, we unravel the generalized involvement of the beta-catenin-driven machinery in the stabilization of EGF-induced mRNAs, including the cancer stem cell regulator IL6. Our study highlights the crucial role of post-transcriptional mechanisms in the maintenance/acquisition of cancer stem cell features and suggests that the hindrance of cytoplasmic beta-catenin function may represent an unprecedented strategy for targeting breast cancer stem/basal-like cells.
| S-EPMC3829939 | biostudies-literature
Project description:Activation of the p53 tumor suppressor triggers a transcriptional program to control cellular response to stress. However, the molecular mechanisms by which p53 controls gene transcription are not completely understood. Here, we uncover the critical role of spatio-temporal genome architecture in this process. We demonstrate that p53 drives direct and indirect changes in genome compartments, topologically associating domains, and DNA loops prior to one hour of its activation, which escort the p53 transcriptional program. Focusing on p53-bound enhancers, we report 340 genes directly regulated by p53 over a median distance of 116 kb, with 74% of these genes not previously identified. Finally, we showcase that p53 controls transcription of distal genes through newly formed and pre-existing enhancer-promoter loops in a cohesin dependent manner. Collectively, our findings demonstrate a previously unappreciated architectural role of p53 as regulator at distinct topological layers and provide a reliable set of new p53 direct target genes that may help designs of cancer therapies.
| S-EPMC10984980 | biostudies-literature