Similar Datasets
Project description:Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth-factor (EGF) and platelet-derived growth-factor (PDGF) receptors are frequently amplified and/or possess gain-of-function mutations in these tumors. Despite years of research into tyrosine-kinase inhibitors, clinical trials have shown disappointing efficacy. One of the underlying reasons is intra-tumor heterogeneity. To assess the effect of intra-tumor heterogeneity on gene expression, we derived a general approach to map single-cell expression profiles to sequentially-acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high-resolution phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics during tumor evolution. A deletion in a PDGF-receptor domain involved in dimerization correlated to an up-regulation of the PI3K/AKT pathway in a proneural GBM, and ectopic expression of this mutant PDGFRA in vitro enhanced proliferation and invasiveness. Descending the phylogenetic tree of the PDGFR-driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor-like cell type that expresses growth and angiogenic factors. In contrast, phylogenetic analysis of an EGFR-amplified tumor showed a gradual up-regulation of pro-invasive genes.
| EGAS00001001900 | EGA
Project description:Overall study: Identification of PDGF-dependent patterns of gene expression in U87 glioblastoma cells. RNA was obtained from triplicate dishes of 5 different groups of U87 cells, each (total 15) analyzed with one U95 microarray chip. Three different comparisons were made: 1) Clone 3.1 (34580-34582) vs. clone 3.3 (34583-34585) vs. parent U87 (34592-34594). Purpose: demonstrate that the gene expression profiles between these 3 cell lines are not different, so they could be pooled as a single untreated group. 2) Pooled control group (34580-34585, 34592-34594) vs. clone 8.1 (34586-34588). Purpose: identify genes specifically controlled by autocrine PDGF activity. 3) Clone 8.1 (34586-34588) vs. clone 8.1 treated with PDGF (34589-34591) Purpose: Identify genes specifically induced by exogenous PDGF. Keywords = platelet-derived growth factor Keywords = glioblastoma Keywords = brain cancer Keywords = sterol regulatory element binding protein Keywords = SREBP Keywords: ordered
2004-12-10 | GSE1923 | GEO
Project description:Background:Mouse models of glioblastoma (GBM), the most aggressive primary brain tumor, are critical for understanding GBM pathology and can contribute to the preclinical evaluation of therapeutic agents. Platelet-derived growth factor (PDGF) signaling has been implicated in the development and pathogenesis of GBM, specifically the proneural subtype. Although multiple mouse models of PDGF-driven glioma have been described, they require transgenic mice engineered to activate PDGF signaling and/or impair tumor suppressor genes and typically represent lower-grade glioma. Methods:We designed recombinant lentiviruses expressing both PDGFB and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following stereotactic injection into the dentate gyrus of adult immunocompetent mice. We engineered these viruses to coexpress CreERT2 with PDGFB, allowing for deletion of floxed genes specifically in transduced cells, and designed another version of this recombinant lentivirus in which enhanced green fluorescent protein was coexpressed with PDGFB and CreERT2 to visualize transduced cells. Results:The dentate gyrus of injected mice showed hypercellularity one week post-injection and subsequently developed bona fide tumors with the pathologic hallmarks of GBM leading to a median survival of 77 days post-injection. Transcriptomic analysis of these tumors revealed a proneural gene expression signature. Conclusion:Informed by the genetic alterations observed in human GBM, we engineered a novel mouse model of proneural GBM. While reflecting many of the advantages of transgenic mice, this model allows for the facile in vivo testing of gene function in tumor cells and makes possible the rapid production of large numbers of immunocompetent tumor-bearing mice for preclinical testing of therapeutics.
| S-EPMC5817944 | biostudies-literature
Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma. Total RNA was obtained from untreated and Dox treated PDGF-driven glioma spheroid cells (PDGF-GSC) which had been isolated from the Gfap-tTa/Tre-PDGFB mouse model used in our study. The data were analyzed to determine the genes that are regulated by PDGF signaling in PDGF-driven glioma.
2016-03-22 | E-GEOD-77419 | biostudies-arrayexpress
Project description:Glioblastoma is the most common type of malignant brain tumor among adults. We used single-cell RNA sequencing (scRNA-seq) to analyze the diversity of glioblastoma cells.
2024-07-25 | GSE214966 | GEO
Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma. Total RNA obtained from PDGF-driven glioma spheroid cells (PDGF-GSC) and primary tumors arising in the Gfap-tTa/Tre-PDGFB mouse model used in our study was analyzed to determine to which subtype of GBM these specimens belonged.
2016-03-22 | E-GEOD-77423 | biostudies-arrayexpress
Project description:The trascription profiles of PDGF-B and EGFRvIII induced glioma models were compared. We show that both models converge towards a phenotype that resembles proneural glioblastoma subset.
2019-06-25 | GSE133095 | GEO
Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
2016-03-22 | GSE77423 | GEO
Project description:Identification of critical survival determinants of PDGF-driven proneural glioma. Results provided information about the genes and pathways that are regulated by PDGF signaling in PDGF-driven proneural glioma and led to the assessment of the importance of the USP1-ID2 axis in proneural glioma.
2016-03-22 | GSE77419 | GEO