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PROVIDER: PRJNA253925 | ENA |
REPOSITORIES: ENA
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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:Aberrant differentiation of glioma stem cells: Implications for therapeutic targeting [Xenograph]
| PRJNA253929 | 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: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 | GSE58923 | GEO
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 | GSE58922 | GEO
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
Project description:In this study, we combined a genome-wide analysis of the Polycomb protein Bmi1 and an in vivo RNAi screening to identify critical targets whose repression in neural progenitor and Malignant Glioma cells enables normal and aberrant self-renewal. Bmi1 ChIP-sequencing generated in 2 primary adult mouse Neural Progenitor cell lines, 1 mouse astrocytic cell line, 1 mouse Glioma initiating cell line, and 1 mouse Glioma cell line. In human cell lines, Bmi1 ChIP-seq was performed for foetal Neural Progenitor Cells, and 2 Glioblastoma Stem-like cells. ChIP-seq for AP-1 in one Glioblastoma stem-like cell line. ChIP-sequencing were generated using either Illumina GxII or HiSeq. We have further performed RNA-seq of adult Ink4a/Arf -/-;BMI1or GFP dox-inducible shRNA mNPC with a doxycycline inducible shRNA targeting BMI1 or GFP (as control). These cells were either treated with doxyclyine for 48h to ablate BMI1 and GFP expression or further subjected to short-term differentiation using either BMP4 (10ng/ml or 50ng/ml for 3 or 6hrs), or FBS (1 or 10% for 3 or 6hrs). Additional mouse RNA-seq were performed in two biological replica of adult mouse brains (littermate) with either wild-type FVB background or BMI1 -/-. Finally, we performed RNA-seq in human Glioblastoma stem-like cells (most likely belonging to the mesenchymal GBM subtype) treated with BMP7, Arvanil and doxycycline or EtOH treated as ctrl.
2013-05-21 | E-GEOD-33912 | biostudies-arrayexpress