Gene expression profiling of Glioma Stem Cells (GSCs) and their differentiated cell counterparts after MG132 treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE62356 | GEO | 2014/10/15
SECONDARY ACCESSION(S): PRJNA263906
REPOSITORIES: GEO
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Project description:Analysis of genes in GSCs and differentiated cells that are induced by MG132 treatment. Total RNAs were isolated from GSCs and differentiated cells after MG132 or DMSO treatment for 6 hrs in serum-free media
2014-10-15 | E-GEOD-62356 | biostudies-arrayexpress
Project description:Glioma-derived stem-like cells (GSCs) are hypothesized to provide a repository of cells in tumors that can self-replicate and be resistant to radiation and chemotherapeutic agents developed for the treatment of tumors. The potential lack of response of GSCs to traditional cytotoxic and radiation therapies has significant implications for tumor biology and therapeutics. At M.D. Anderson Cancer Center, a large number of GSC lines representing several glioma sub-types have been isolated and characterized with respect to gene expression. In order to identify potential therapeutic targets relating to GSC phenotype, we examined protein expression in 35 GSC lines relative to an external protein standard using label-free quantitative proteomics. Samples were analyzed in triplicate by nanoLC-MS/MS (Orbitrap Elite, Thermo) in block-randomized groups of three GSCs plus the external standard. The resulting .raw files were aligned by group in Progenesis LC-MS (Nonlinear Dynamics). Database searching was performed with PEAKS 6 software (BSI) against a UniprotKB/SwissProt Human database appended with the cRAP contaminant database. Peptide intensities were exported for analysis in DanteR. The resulting relative fold changes were used to drive unsupervised hierarchical clustering of the cell lines for the purpose of classifying cell lines, and Ingenuity Pathway Analysis (IPA) and the DAVID webtool were used to determine the biochemical pathways and biological processes impacted by protein changes in each cell line. Within IPA, Upstream Analysis was used to predict biological functions and transcriptional regulators whose increased or decreased activity was consistent with the observed fold changes, and the resulting upstream regulators with significant z-scores were exported for unsupervised hierarchical clustering. In addition to showing upstream regulators known to be associated with glioma, including Myc, tumor protein 53 (TP53), N-myc proto-oncogene protein (MYCN), two novel upstream regulators, synoviolin 1 (SYVN1) and interleukin 5 (IL5) were identified. A cluster of proteins found to be decreased relative to mixed control in mesenchymal cell lines was subjected to further bioinformatics analysis, identifying SRSF2 as a potential upstream regulator.
2015-07-07 | PXD001890 | Pride
Project description:RNA deep sequencing analysis of glioma stem cells(GSCs) and non-GSCs
| PRJNA423102 | ENA
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:Analysis of Hoechst 33342 dye-effluxing side population cells (SP cells defined as glioma stem cells, GSCs) and dye-retaining main population cells (MP cells defined as non-GSCs) that were FACS-sorted from the C6 glioma cell line stably expressing EGFP (C6-eGFP). ECM-related genes, such as Col4a1 and Col4a2, and the iron carrier gene Tf are upregulated in MP cells. Results provide the insight into molecular basis underlying the maintenance of GSCs by non-GSCs. Gene expression profiles were compared between SP and MP cells just after FACS-sorting from the whole C6-eGFP cells based on their Hoechst-effluxing abilities.
2016-07-03 | E-GEOD-72431 | biostudies-arrayexpress
Project description:Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. The glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes and in particular ALDH1A3, were enriched in Mes GSCs. Glycolytic activity and ALDH activity were significantly elevated in Mes GSCs but not in PN GSCs. Expression of ALDH1A3 was also increased in clinical HGG compared with low-grade glioma or normal brain tissue. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs. Last, radiation treatment of PN GSCs up-regulated Mes-associated markers and downregulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3- mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature.
2015-03-20 | GSE67089 | GEO
Project description:Analysis of Hoechst 33342 dye-effluxing side population cells (SP cells defined as glioma stem cells, GSCs) and dye-retaining main population cells (MP cells defined as non-GSCs) that were FACS-sorted from the C6 glioma cell line stably expressing EGFP (C6-eGFP). ECM-related genes, such as Col4a1 and Col4a2, and the iron carrier gene Tf are upregulated in MP cells. Results provide the insight into molecular basis underlying the maintenance of GSCs by non-GSCs.
2016-01-01 | GSE72431 | GEO
Project description:he unique prolyl isomerase Pin1 that promotes protein conformational changes is a pivotal therapeutic target in many cancers, but little is known about the regulation of Pin1 protein stability. We previously found that Pin1 was highly expressed in glioma stem cells (GSCs) relative to non-stem tumor cells (NSTCs). Interestingly, treatment of the proteasome inhibitor MG132 markedly restored Pin1 protein expression in NSTCs to a level similar to GSCs. We therefore sought to identify the molecular regulators controlling the proteasomal degradation of Pin1 by mass spectrometry analysis of Pin1-interacting proteins in GSCs. The results showed that Pin1 interacts with a deubiquitinase USP34 in GSCs, suggesting that Pin1 may be stabilized by USP34.
2024-01-26 | PXD041043 | Pride
Project description:Using four patient-derived GSCs lines and their induced differentiating counterparts, we performed high-throughput microarray analysis to identify the profile changes of lncRNAs and mRNAs. The differentiation status was determined by Immunofluorescence and qRT-PCR.
2019-04-17 | GSE68343 | GEO
Project description:Glioblastoma multiforme (GBM) is a highly lethal brain tumor. Due to resistance to current therapies, patient prognosis remains poor and development of novel and effective GBM therapy is crucial. Glioma stem cells (GSCs) have gained attention as therapeutic target in GBM due to their relative resistance to current therapies and potent tumor-initiating ability. Recent studies including our own identified that the mitotic kinase, maternal embryonic leucine-zipper kinase (MELK), is highly expressed in GBM tissues, specifically in GSCs, and its expression is inversely correlated with the post-surgical survival period of GBM patients. In addition, patient-derived GSCs depend on MELK for their survival and growth both in vitro and in vivo. Here, we provide evidence that the kinase activity of MELK is essential for the action of MELK in GSCs and vital for GBM growth. We utilized in silico structure-based analysis for protein-compound interaction to predict that a recently identified small molecule, Compound 1 (C1), binds to the kinase-active site of MELK protein and eliminates MELK kinase activity in nanomolar concentrations. When treated with C1, GSCs undergo mitotic arrest and subsequent cellular apoptosis in vitro, a phenotype identical to that observed using MELK shRNA-mediated knockdown. C1 treatment strongly induces tumor cell apoptosis in slice cultures of GBM surgical specimens and attenuates growth of mouse intracranial tumors derived from GSCs in a dose-dependent manner. Lastly, C1 treatment sensitizes GSCs to radiation treatment. Collectively, these data indicate that targeting MELK kinase activity is a promising approach to attenuate GBM growth by eliminating GSCs in tumors. Microarray-based expression analysis of glioma stem cells treated with MELK-signaling inhibitors
2013-08-28 | E-GEOD-50227 | biostudies-arrayexpress