The translatome of Glioblastoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229866 | GEO | 2023/08/01
REPOSITORIES: GEO
Similar Datasets
Project description:SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM. SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM. 4 treatments
2013-08-15 | E-GEOD-49162 | biostudies-arrayexpress
Project description:SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM. SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM. Gene expression data for 17 isolated Glioma Stem Cells
2013-08-15 | E-GEOD-49161 | biostudies-arrayexpress
Project description:SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM. SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM.
2013-08-15 | GSE49162 | GEO
Project description:SUMMARY Despite numerous genome-wide association studies involving glioblastoma (GBM), few therapeutic targets have been identified for this disease. Using patient derived glioma sphere cultures (GSCs), we have found that a subset of the proneural (PN) GSCs undergo transition to a mesenchymal (MES) state in a TNFa/NFkB dependent manner with an associated enrichment of CD44 sub-populations and radio-resistant phenotypes. To the contrary, MES GSCs exhibit constitutive NFkB activation, CD44 enrichment and radio-resistance. Patients whose tumors exhibit a higher MES metagene, increased expression of CD44, or activated NFkB were associated with poor radiation response and shorter survival. Our results indicate that NFkB activation mediated MES differentiation and radiation resistance presents an attractive therapeutic target for GBM. SIGNIFICANCE In this study, we show plasticity between the proneural (PN) and mesenchymal (MES) transcriptome signatures observed in glioblastoma (GBM). Specifically, we show that PN glioma sphere cultures (GSCs) can be induced to a MES state with an associated enrichment of CD44 expressing cells and a gain of radio-resistance, which we implicate as NFkB- dependent. Newly diagnosed GBM samples show a direct correlation between radiation response, higher MES metagene, CD44 expression, and NFkB activation. This correlation is also observed in the subset of GBM samples that do not exhibit IDH1 mutation, a favorable prognostic marker. Our results uncover a previously unknown link between subtype plasticity that is regulated by NFkB. Inhibition of NFkB activation can directly impact radio-resistance and presents an attractive therapeutic target for GBM.
2013-08-15 | GSE49161 | GEO
Project description:The subset of GBM patient samples gives rise to adherent cultures even in sphere culture conditions. Most samples in this subset are tumorigenic and exhibit a hybrid expression profile when tested with the marker panel. Cultures from these samples have a predominantly mesenchymal character based on substrate adherence, morphology, differentiation potential and gene expression. Total RNA isolated from glioblastoma stem cells (GSC) cultured as spheres was compared to that from adherent GSCs cultured in sphere culture conditions that exhibited both GSC and mesenchymal properties.
2016-07-21 | E-GEOD-74571 | biostudies-arrayexpress
Project description:Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NFκB was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NFκB signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NFκB target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NFκB pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NFκB may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation. Gene expression in differentiated cells relative to stem cells in three different glioblastoma cultures
2011-03-01 | E-GEOD-20736 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of glioma sphere-forming cells (GSC) derived from surgery specimens of glioblastoma patients.The Illumina Infinium 450K Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 450,000 CpGs in 12 GSC samples. Clonogeneic assays were used to detemine the radiation response of these 12 GSCs.
2016-10-06 | GSE75443 | GEO
Project description:Prognosis of glioblastoma remains poor despite a great deal of research. In glioblastoma, the existence of glioblastoma stem cells (GSCs) has been shown, which are responsible for tumorigenesis, invasive capacity, and therapy resistance. One of cancer stem cell markers, Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) plays a role in maintenance of GSCs, however, properties of the Lgr5 positive GSCs have not been fully understood. We applied the Sleeping-Beauty transposon-induced glioblastoma model to the Lgr5-GFP transgenic mice and sorted the GFP-positive cells from the neurosphere cultures derived from the mouse glioblastoma tissues. We found that the GFP-positive GSCs exhibited higher expression of Gli2 using a global gene expression analysis.
2020-08-25 | GSE156739 | GEO
Project description:To identify receptors and pathways active in glioblastoma (GBM) stem like cells (GSCs), we generated and screened thousands of monoclonal antibodies (mAbs) for preferential binding to primary cultures enriched in GSCs. This led to the identification of the integrin alpha 7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression was negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses demonstrated a key biological function of ITGA7 in growth and invasion of GSCs. In addition, we showed that targeting ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling and led to a significant delay of tumor engraftment and strong reduction in size and invasion. Our data underline the potential value of ITGA7 as glioma biomarker and therapeutic target.
2018-01-10 | PXD006069 | Pride
Project description:Patient-derived primary GSCs were established from discarded specimens obtained from glioblastoma (GBM) patients undergoing surgery at UT Health San Antonio. We examined global transcriptional changes by RNA-sequencing using patient derived glioma stem cells (GSCs) transduced with either control shRNA or Reticulocalbin-3 (RCN3) shRNA. RNA-seq studies showed downregulation of genes related to translation, ribosome, and cytokine signaling and upregulation of genes related to immune response, stem cell differentiation, and extracellular matrix.
2023-04-19 | GSE226990 | GEO