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PROVIDER: PRJNA253925 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting [Xenograph]
| PRJNA253929 | ENA
Project description:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting (shift)
| PRJNA253927 | ENA
Project description:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting (GSCs)
| PRJNA253928 | ENA
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212700 | GEO
Project description:Diffuse midline gliomas (DMGs) are uniformly fatal pediatric central nervous system cancers, refractory to standard of care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3.3 and H3.1, K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape, which we interrogated here for epigenetic dependencies using a CRISPR screen in patient-derived H3K27M-glioma neurospheres. We show that H3K27M-glioma cells are dependent on core components of the mammalian SWI/SNF (BAF) chromatin remodeling complex for maintaining glioma stem cells in a cycling, oligodendrocyte precursor cell (OPC)-like state. Genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacological suppression opposes proliferation, promotes differentiation, and improves overall survival of patient-derived xenograft (PDX) models. In summary, we demonstrate that therapeutic inhibition of BAF complex has translational potential for children with H3K27M-gliomas.
2022-09-15 | GSE212679 | GEO
Project description:Glioma initiating cells/stem cells exist in the bulk tumor of glioblastoma. This cell population contributes to the frequent resistances toward radiation/chemotherapy, aggressiveness of adult brain cancer and increased recurrence rate. Targeting stem cell population becomes one the most promising and permissive therapeutic strategies. We isolated glioma stem cells from patient-derived xenografts and profiled their epigenomic features, including 4 different DNA marks and 2 enhancer marks, and transcriptome in these in vitro cultured cell lines. Three fetal brain-derived neural stem/progenitors cells were used for comparing the unique and common molecular features in these glioma cancer stem cells.
2018-02-23 | GSE92462 | GEO
Project description:Glioma initiating cells/stem cells exist in the bulk tumor of glioblastoma. This cell population contributes to the frequent resistances toward radiation/chemotherapy, aggressiveness of adult brain cancer and increased recurrence rate. Targeting stem cell population becomes one the most promising and permissive therapeutic strategies. We isolated glioma stem cells from patient-derived xenografts and profiled their epigenomic features, including 4 different DNA marks and 2 enhancer marks, and transcriptome in these in vitro cultured cell lines. Three fetal brain-derived neural stem/progenitors cells were used for comparing the unique and common molecular features in these glioma cancer stem cells.
2018-02-23 | GSE92460 | GEO
Project description:Glioma initiating cells/stem cells exist in the bulk tumor of glioblastoma. This cell population contributes to the frequent resistances toward radiation/chemotherapy, aggressiveness of adult brain cancer and increased recurrence rate. Targeting stem cell population becomes one the most promising and permissive therapeutic strategies. We isolated glioma stem cells from patient-derived xenografts and profiled their epigenomic features, including 4 different DNA marks and 2 enhancer marks, and transcriptome in these in vitro cultured cell lines. Three fetal brain-derived neural stem/progenitors cells were used for comparing the unique and common molecular features in these glioma cancer stem cells.
2018-02-23 | GSE92459 | GEO
Project description:Analysis of the effects of targeting NOS2 at the gene expression level. Our studies demonstrated a role for NOS2 in glioma biology through the maintenance of the glioma stem cell phenotype. Microarray results provide novel targets of NOS2 and suggest mechanisms through which NOS2 contributes to glioma stem cell biology. Glioma stem cells isolated from two different human glioma xenografts were infected with a non-targeting control shRNA or two different shRNAs directed against NOS2 (each treatment in each tumor performed in technical duplicates).
2011-07-08 | E-GEOD-29750 | biostudies-arrayexpress
Project description:SUMMARY Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs. SIGNIFICANCE Terminal differentiation has been proposed as a therapeutic strategy for glioblastoma (GBM). Culturing of GBM derived tumor initiating glioma stem cells (GSCs) in fetal bovine serum containing media is a proposed mode of differentiation that is thought to induce loss of stem cell characteristics, promote neural lineage differentiation and a parallel loss of tumor initiation capacity. Here we show that GSCs retained both neurosphere formation and tumor initiation abilities after short or long term serum exposure. Under serum induced differentiating conditions, GSCs expressed both neural lineage and stem cell markers, highlighting the aberrant pseudo-differentiation state. GSCs maintained under adherent differentiating conditions continued to proliferate and initiate tumor formation with efficiencies similar to GSCs maintained under proliferating (neurosphere) conditions. Proneural (PN) GSCs under serum exposure showed an induction of mesenchymal (MES) gene expression signatures. Our data indicate that the tumor initiation ability of GSCs is independent of their differentiation state and that terminal differentiation as a therapeutic approach may not effectively negate tumorigenicity of GSCs.
2015-09-01 | GSE58921 | GEO