Single cell RNA-sequencing of GSCs and GBM tumours
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PROVIDER: EGAS00001004656 | EGA |
REPOSITORIES: EGA
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Project description:Characterization of glioblastoma tumors and glioblastoma stem cells (GSCs) lines via RNA-seq and/or WGS profiling.
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Project description:Glioblastoma stem cells (GSCs) have been implicated in tumor initiation, progression and resistance to therapy. We investigated the expression, function, mechanisms of action and therapeutic targeting of T-type calcium channels (Cav3.2) with the FDA approved and repurposed drug mibefradil in glioblastoma (GBM), and GSCs. We found that Cav3.2 is highly expressed in human GBM specimens and enriched in GCSs. Analyses of TCGA and REMBRANDT databases confirmed the upregulation of Cav3.2 in a subset of tumors (TCGA) and showed that overexpression is associated with worse prognosis. Mibefradil and Cav3.2 knockdown inhibited the growth, survival and stemness of GSCs and sensitized them to temozolomide (TMZ) chemotherapy. To investigate the mechanisms of action of Cav3.2 in GSC, we performed proteomic and transcriptomic screenings followed by functional rescue experiments. Inhibition of Cav3.2 altered cancer signaling pathways and gene transcription. Among other, inhibition of Cav3.2 suppressed GSC growth through inhibition of pro-survival pathways AKT/mTOR, and induction of apoptosis through upregulation of survivin, BAX and cleavage of caspase 9 and PARP. Inhibition of Cav3.2 induced a decrease in the expression of oncogenes including PDGFA, PDGFB and TGFB1 and an increase in the expression of tumor suppressors including TNFRSF14 and HSD17B14. In vivo oral administration of Cav3.2 blocker mibefradil significantly inhibited GSC-derived xenograft growth, prolonged animal survival and sensitized the tumors to TMZ. Our study represents the first comprehensive characterization of Cav3.2 in GBM tumors and GSC. The findings establish Cav3.2 inhibition with the repurposed FDA-approved drug mibefradil as a new strategy for GBM therapy.
2017-08-31 | GSE95106 | GEO
Project description:The heterogeneous nature of glioblastoma stem-like cells (GSCs) creates hurdles in developing effective therapies against glioblastoma, making it extremely difficult to eradicate. In this part of the project, we investigated the potential role of GSCs-derived small extracellular vesicles (sEVs) in glioblastoma heterogeneity, plasticity, and aggressiveness with the particular focus on their complexity in term of proteins. Proteome profiling of sEVs and their respective cell lines showed that GSCs-derived sEVs retain their subtype characteristics and are enriched in proteins playing a role in amino acids, carboxylic acids, organic acids transmembrane transport, and growth factor binding. In summary, we revealed the protein content of GSCs-derived sEVs and unveiled their potential contribution to tumor heterogeneity and critical cellular processes commonly deregulated in glioblastoma.
2024-05-21 | PXD036359 | Pride
Project description:Characterization of gene expression for a panel of 50 in vitro and in vivo models of glioblastoma (GBM). Models include subcutaneously established xenograft lines, orthotopically grown subcutaneously established xenograft lines, serum derived cell lines and stem cell media derived cell lines. Multiple replicates of each line were run on different dates to determine the effect of batch and processing date on reproducibility of gene expression profiles 117 samples analyzed from 50 distinct GBM xenografts or cell lines. Biological replicates from the same passage number were included for many, but not all, of the lines.
2011-12-01 | E-GEOD-26344 | biostudies-arrayexpress
Project description:Glioblastoma stem cells (GSCs) fate is controlled by environmental cues, among which cytokines play a crucial role. The transforming growth factor β (TGFβ) family signaling pathways controls GSCs. On one hand, TGFβ promotes cell proliferation in GBM, it induces the expression of platelet-derived growth factor-B (PDGFB). Moreover, TGFβ, via its signaling mediators Smad2/3, induces the expression of the cytokine leukemia inhibitory factor (LIF) and Sox4, which in turn enhances the expression of the stem cell transcription factor Sox2; this increases the self-renewal capacity of the GSCs and their stemness characteristics, and enhances the GSC tumor-initiating potential. On the other hand, Bone morphogenic proteins (BMPs) are known to promote GSC differentiation towards the astrocytic phenotype. To further understand which genes are regulated by TGFβ and BMP7 in GSCs we performed a microarray in the Affymetrix HTA2 platform in three different glioblastoma cell line, U2987, and two patient-derived glioblastoma stem cells, U3031MG and U3034MG, in the presence or absence of 5 ng/ml of TGFβ or 30 ng/ml BMP7 for 24 h, three biological replicates per condition.
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Project description:Characterization of gene expression for a panel of 50 in vitro and in vivo models of glioblastoma (GBM). Models include subcutaneously established xenograft lines, orthotopically grown subcutaneously established xenograft lines, serum derived cell lines and stem cell media derived cell lines. Multiple replicates of each line were run on different dates to determine the effect of batch and processing date on reproducibility of gene expression profiles
2011-12-01 | GSE26344 | 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:Although tumor-propagating cells can be derived from glioblastomas (GBMs)of theproneural and mesenchymal subtypes,a gliomastem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/orproneural GSCs (pGSCs) alone are sufficient to generate the heterogeneity observed in GBM.We performed single-cell/nuclei RNA-sequencing of 28 gliomas, and single-cell ATAC-sequencing for8 cases. We find that GBM GSCs reside ona single axis of variation, rangingfrom proneural to mesenchymal. In silico lineage tracing using both transcriptomics and genetics supports mGSCs as the progenitors of pGSCs.Dual inhibition of pGSC-enrichedand mGSC-enrichedgrowth and survival pathways provides a more complete treatment thancombinations targetingone GSC phenotype alone.This study sheds light on a long-standing debate regarding lineage relationships among GSCs and presents a paradigm by which personalized combination therapies can be derived from single-cell RNA signatures, to overcome intra-tumor heterogeneity.
2019-10-12 | GSE138794 | GEO
Project description:It has been previously described that in glioblastoma (GBM), BMPs deplete the tumorigenic potential of glioblastoma stem cells (GSCs), promoting their differentiation towards the astrocytic lineage. To gain more insight on how BMPs regulate differentiation in GSCs, we are interested in identifying new BMP target genes in GBM cells. To this end, the patient derived glioblastoma cell lines U3031MG and U3034MG were stimulated or not with 30ng/ml BMP7 for 2 and 24 h, total RNA was isolated from three biological replicates per condition, and a microarray screen with the Affymetrix U133plus2 platform was performed.
2021-05-01 | E-MTAB-9811 | 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