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GSE12836
Mus musculus
3 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We analyzed the generation of mouse gliomas following the overexpression of PDGF-B in embryonic neural progenitors. Comparison of our microarray data, with published gene expression data sets for many different murine neural cell types, revealed a closest relationship between our tumor cells and oligodendrocyte progenitor cells, confirming definitively that PDGF-B-induced gliomas are pure oligodendrogliomas.
Publication Title
PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic. We showed that glioma cells are able to progress towards a high-grade phenotype even in immunodeficient mice, albeit more slowly and this progression invariably requires a downregulation of immunostimulatory genes.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic.
Publication Title
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
We recently described TRIM8, a nuclear E3 ubiquitin ligase, whose expression inversely correlates with glioma grade. TRIM8 restoration suppresses cell growth and induces a significant reduction of clonogenic potential in both U87MG glioblastoma and patients' primary glioma cell lines. Since E3 ubiquitin ligase proteins regulate carcinogenesis through the timely control of many cellular processes such as DNA damage response, metabolism, transcription, and apoptosis, we reasoned that TRIM8 activity might impact on cell transcriptome patterns, thereby promoting cancer development and progression. Therefore, we profiled the whole transcriptome of normal embryonic neural stem cells (eNSC) infected with a retrovirus expressing FLAG-Trim8 by using RNA-Seq. RNA-Seq revealed 1365 differentially expressed transcripts of 912 genes. 723 of them (corresponding to 648 RefSeq genes) differed significantly of at least 1.5 folds (192 upregulated transcripts of 178 genes and 531 downregulated transcripts of 470 genes). 80 genes, among all differentially expressed genes, resulted to significantly enrich 18 pathways by IPA analysis. 53% of these genes (43 out of 80 genes) are related to cell-morphology, cell death and survival, with a preponderantly representation of signaling pathways related to neurotransmission and to CNS, including axonal guidance, GABA Receptor, ephrin B, synaptic long-term potentiation/depression, and glutamate receptor. Specifically, our results substantiate the role of TRIM8 in the brain functions through the dysregulation of genes involved in different pathways, including JAK-STAT. Finally, we provided additional evidence about the existence of a functional interactive crosstalk between TRIM8 and STAT3 with possible implications in the development and progression of glioma. Overall design: Profiling the transcriptome of TRIM8-expressing primary mouse embryonal neural stem cells using RNA-Seq
Publication Title
TRIM8-driven transcriptomic profile of neural stem cells identified glioma-related nodal genes and pathways.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The response of cells to hypoxia is characterised by co-ordinated regulation of many genes. Studies of the regulation of the expression of many of these genes by oxygen has implicated a role for the heterodimeric transcription factor hypoxia inducible factor (HIF). The mechanism of oxygen sensing which controls this heterodimeric factor is via oxygen dependent prolyl and asparaginyl hydroxylation by specific 2-oxoglutarate dependent dioxygenases (PHD1, PHD2, PHD3 and FIH-1). Whilst HIF appears to have a major role in hypoxic regulation of gene expression, it is unclear to what extent other transcriptional mechanisms are also involved in the response to hypoxia. The extent to which 2-oxoglutarate dependent dioxygenases are responsible for the oxygen sensing mechanism in HIF-independent hypoxic gene regulation is also unclear. Both the prolyl and asparaginyl hydroxylases can be inhibited by dimethyloxalylglycine (DMOG). Such inhibition can produce activation of the HIF system with enhanced transcription of target genes and might have a role in the therapy of ischaemic disease. We have examined the extent to which the HIF system contributes to the regulation of gene expression by hypoxia, to what extent 2-oxoglutarate dependent dioxygenase inhibitor can mimic the hypoxic response and the nature of the global transcriptional response to hypoxia. We have utilised microarray assays of mRNA abundance to examine the gene expression changes in response to hypoxia and to DMOG. We demonstrate a large number of hypoxically regulated genes, both known and novel, and find a surprisingly high level of mimicry of the hypoxic response by use of the 2-oxoglutarate dependent dioxygenase inhibitor, dimethyloxalylglycine. We have also used microarray analysis of cells treated with small interfering RNA (siRNA) targeting HIF-1alpha and HIF-2alpha to demonstrate the differing contributions of each transcription factor to the transcriptional response to hypoxia. Candidate transcripts were confirmed using an independent microarray platform and real-time PCR. The results emphasise the critical role of the HIF system in the hypoxic response, whilst indicating the dominance of HIF-1alpha and defining genes that only respond to HIF-2alpha.
Publication Title
Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Systemic sclerosis (SSc) or scleroderma is a chronic multiorgan autoimmune disease of unknown etiology characterized by vascular, immunological and fibrotic abnormalities. Several lines of evidence have shown that the endocannabinoid system (ECS) may play a role in the pathophysiology of SSc. VCE-004.8, a CBD aminoquinone derivative, is a dual PPAR?/CB2 that alleviates bleomycin (BLM)-induced skin fibrosis. Herein we report that EHP-101, an oral lipidic formulation of VCE-004.8, prevents skin and lung fibrosis and collagen accumulation in BLM challenged mice. Immunohistochemistry analysis of the skin demonstrate that EHP-101 prevents macrophage infiltration, and the expression of Tenascin C (TNC), VCAM, and the a-smooth muscle actin (SMA). In addition, a reduced expression of vascular CD31, paralleling skin fibrosis, was also prevented by EHP-101. RNAseq analysis in skin biopsies showed a clear effect of EHP-101 in the inflammatory and epithelial-mesenchymal transition transcriptomic signatures. TGF-beta regulated genes such as matrix metalloproteinase-3 (Mmp3), cytochrome b-245 heavy chain (Cybb), lymphocyte antigen 6E (Ly6e), vascular cell adhesion molecule-1 (Vcam1) and the Integrin alpha-5 (Itga5) were induced in BLM mice and repressed by EHP-101 treatment. We also intersected differentially expressed genes in EHP-101-treated mice with dataset of human scleroderma intrinsic genes and found 53 overlapped genes, including the C-C motif chemokine 2 (Ccl2) and the interleukin 13 receptor subunit alpha 1 (IL-13Ra1) genes, which have been studied as biomarkers of SSc. Altogether the results indicate that this synthetic cannabinoid qualifies as a novel compound for the management and possible treatment of scleroderma and, potentially, other fibrotic diseases. Overall design: RNA-Seq profiles were generated for six- to eight-week-old female BALB/c mice in three conditions: Control, Bleomycin and Bleomycin + EHP-101 treatment (N=2).
Publication Title
EHP-101, an oral formulation of the cannabidiol aminoquinone VCE-004.8, alleviates bleomycin-induced skin and lung fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Several lines of evidence have shown that the endocannabinoid system (ECS) may play a role in the pathophysiology of systemic sclerosis (SSc). Thereby, structurally different dual PPAR?/CB2 agonists such as VCE-004.8 and Ajulemic acid (AjA) have been shown to alleviate skin fibrosis and inflammation in experimental models of SSc. Since both compounds are currently being tested in humans, we were interested to identify similarities and differences in a murine model of SSc. One method available to assess this is the pharmacotranscriptomic signature of the individual compounds. To analyze the pharmacotranscriptomic signature, we used RNA-Seq to analyze the skin gene expression changes from bleomycin-induced fibrosis in mice treated orally with either AjA or EHP-101, a lipidic formulation of VCE-004.8. While both compounds prevented the upregulation of a common group of genes involved in the inflammatory and fibrotic components of the disease and the pharmacotranscriptomic signatures were similar for both compounds in some pathways, we found key differences between the compounds in several functional groups, including genes related the hypoxia, interferon-a and interferon-? response. Additionally, we found 28 specific genes with translation potential by comparing our results with a list of intrinsic human scleroderma genes. Inmunohistochemical analysis revealed that both EHP-101 and AjA prevented bleomycin-induced skin fibrosis, collagen accumulation, and TNC and VCAM expression. However, only EHP-101 normalized the reduced expression of vascular CD31, CD34 and Von Willebrand factor markers, which parallels skin fibrosis, while AjA did not affect these markers. Finally, clear differences were also found in the plasmatic biomarker analysis, in which we found that EHP-101, but not AjA, enhanced the expression of some factors related to angiogenesis and vasculogenesis. Altogether the results indicate that dual PPAR?/CB2 agonists qualify as a novel therapeutic approach for the treatment of SSc and other fibrotic diseases as well, and that EHP-101 has unique mechanisms of action related to the pathophysiology of SSc which could be beneficial in treatment of this complex disease with no current therapeutic options. Overall design: RNA-Seq profiles were generated for six- to eight-week-old female BALB/c mice in four conditions: Control, Bleomycin, Bleomycin + EHP-101 treatment and Bleomycin + Ajulemic acid treatment. Please note that the "raw_counts_newsamples.txt" includes raw counts obtained from featureCounts for the samples included in this entry and the "raw_counts_merged.txt" includes raw counts obtained from merging the counts of the samples from this entry with the counts of the samples from the GSE115503 entry.
Publication Title
Cannabinoid derivatives acting as dual PPARγ/CB2 agonists as therapeutic agents for systemic sclerosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The overall cellular response to oxidative stress generated by Ero1 in the lumen of the mammalian endoplasmic reticulum (ER) is poorly characterized. Here, we investigate the effects of overexpressing a hyperactive mutant (C104A/C131A) of Ero1.
Publication Title
Hyperactivity of the Ero1α oxidase elicits endoplasmic reticulum stress but no broad antioxidant response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
MiR-1246 was found to promote tumorigenesis and metastasis in sevearl cancer types. In the context of tumor microenvironment, tumor-associated macrophages are a central part typically correlated with poor prognosis.
Publication Title
Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.
Sample Metadata Fields
Specimen part
View Samples