Glioblastoma Hijacks Microglial Gene Expression to Support Tumor Growth
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA417971 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6281550_1.fastq.gz | Fastqsanger.gz | |||
| SRR6281550_2.fastq.gz | Fastqsanger.gz | |||
| SRR6281560_1.fastq.gz | Fastqsanger.gz | |||
| SRR6281560_2.fastq.gz | Fastqsanger.gz | |||
| SRR6281570_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 83 |
Similar Datasets
Project description:Background Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells. Methods We used RNASeq to analyze the expression patterns of genes involved in key microglial function of microglia in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor. Results We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma. Conclusion Our data define a MicrogliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion and enhancing tumor propagation. For further exploration we developed an interactive online tool at www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.
2020-04-22 | GSE106775 | GEO
Project description:BackgroundGlioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells.MethodsWe used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor.ResultsWe show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma.ConclusionOur data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.
| S-EPMC7164149 | biostudies-literature
Project description:Tumor-Associated Microglia Secrete Extracellular ATP to Support Glioblastoma Progression
| PRJNA1150205 | ENA
Project description:Clemastine suppresses proneural glioblastoma stem cell growth
| PRJNA773389 | ENA
Project description:Clemastine suppresses proneural glioblastoma stem cell growth II
| PRJNA773719 | ENA
Project description:Mycobacterium tuberculosis hijacks host primary transcripts
| PRJNA393396 | ENA
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.
2020-09-01 | E-MTAB-9076 | biostudies-arrayexpress
Project description:We have previously determined the insulin-like growth factor 1 receptor (IGF1R) to be amplified and overexpressed in paediatric glioblastoma. In order to probe the efficacy and mechanisms of action of various inhibitors of the receptor, we have carried out expression profiling of paediatric glioblastoma cells treated with 5x IC50 of the compounds PPP and NVP-AEW541 over a 24 hour time-course.
2011-01-08 | E-TABM-889 | biostudies-arrayexpress
Project description:Glioblastoma ranks among the most aggressive and lethal of all human cancers. Functionally defined glioma stem cells (GSCs) contribute to this poor prognosis by driving therapeutic resistance and maintenance of cellular heterogeneity. To understand the molecular processes essential for GSC maintenance and tumorigenicity, we interrogated the super-enhancer landscapes of primary glioblastoma specimens and in vitro GSCs. GSCs epigenetically upregulated ELOVL2, a key polyunsaturated fatty acid synthesis enzyme. Targeting ELOVL2 inhibited glioblastoma cell growth and tumor initiation. ELOVL2 depletion altered cellular membrane phospholipid composition, disrupted membrane structural properties, and diminished EGFR signaling through control of fatty acid elongation. In support of the translational potential of these findings, dual targeting of polyunsaturated fatty acid synthesis and EGFR signaling had a combinatorial cytotoxic effect on GSCs.
2019-08-19 | GSE130648 | GEO
Project description:The prevailing view is that myeloid cells in the tumor microenvironment (TME) are immunosuppressive and promote glioblastoma (GBM) progression. However, myeloid cells have the functional plasticity to restrict or support tumor cell growth. TREM2 plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. We found TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in GBM patients. TREM2 loss of function in human macrophages and mouse myeloid cells increased tumoricidal capacity. TREM2 in myeloid cells restricts IFNγ-induced immunoactivation and proinflammatory polarization. In orthotopic mouse GBM models, Trem2-/- mice and mice with acute brain Trem2 reduction demonstrate survival benefit. Trem2 inhibition reprograms myeloid phenotypes and increases PD-1+CD8+ T cells in the TME. Trem2 deficiency enhances the effectiveness of anti-PD-1 treatment and may represent a therapeutic strategy for GBM patients.
2023-05-12 | GSE226292 | GEO