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GSE69072
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human CD8+ T cells are functionally heterogeneous and can be divided into distinct subsets according to CCR7 and CD45RA expression levels. Among the subsets, CCR7-CD45RA+ CD8+ T cells are considered to be terminally differentiated cells and designated as Temra. Temra show attenuated ability to proliferate and produce IFN-gamma in response to TCR stimulation, while Temra show improved function after IL-15 treatment.
Publication Title
IL-15 boosts the function and migration of human terminally differentiated CD8+ T cells by inducing a unique gene signature.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-B, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. A LIF blocking antibody abolished C26 CM-induced STAT reporter activation STAT3 phosphorylation and myotube atrophy, but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked the C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3C-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together these data support an important role of LIF- JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.
Publication Title
A Key Role for Leukemia Inhibitory Factor in C26 Cancer Cachexia.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role of ThPOK in the CD8 T cell response to an acute viral infection. We observed that clonal expansion is significantly less in both primary and secondary CD8 T cell responses in the absence of functional ThPOK. To approach this mechanism, we carried out a microarray analysis for comparison of gene expression between ThPOKhd/hd and ThPOKwt/wt P14 memory T cells.
Publication Title
ThPOK derepression is required for robust CD8 T cell responses to viral infection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
miR-155 is a microRNA associated with poor prognosis in lymphoma and leukemia and has been implicated in the progression of Mycosis Fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). In this study, we developed and tested Cobomarsen (MRG-106), a locked nucleic acid-modified oligonucleotide inhibitor of miR-155. In MF cell lines in vitro, inhibition of miR-155 with Cobomarsen de-repressed direct miR-155 targets, decreased expression of multiple gene pathways associated with cell survival, reduced survival signaling, decreased cell proliferation, and activated apoptosis.
Publication Title
Cobomarsen, an oligonucleotide inhibitor of miR-155, co-ordinately regulates multiple survival pathways to reduce cellular proliferation and survival in cutaneous T-cell lymphoma.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found a new spontaneous mutant mouse, laggard, characterized by general weakness in movements and retardation in growth.
Publication Title
Kif14 mutation causes severe brain malformation and hypomyelination.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Epstein-Barr virus (EBV) has evolved exquisite controls over its host cells, human B lymphocytes, not only directing these cells during latency to proliferate and thereby expand the pool of infected cells, but also to survive and thereby persist for the lifetime of the infected individual. Although these activities ensure the virus is successful, they also make the virus oncogenic, particularly when infected people are immunosuppressed. Here we show, strikingly, that one set of EBV’s miRNAs both sustain BL (Burkitt’s lymphoma) cells in the absence of other viral oncogenes and promote the transformation of primary B lymphocytes. Burkitt’s Lymphoma cells were engineered to lose EBV and found to die by apoptosis and could be rescued by constitutively expressing viral miRNAs in them. Two of these EBV miRNAs were found to target Caspase 3 to inhibit apoptosis at physiological concentrations. Overall design: Examination of RISC associated transcripts under 4 conditions in Sav S1-1 cells
Publication Title
Epstein-Barr virus maintains lymphomas via its miRNAs.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The dendritic cell (DC) is a master regulator of immune responses. Pathogenic viruses subvert normal immune function in DCs through the expression of immune antagonists. Understanding how these antagonists interact with the host immune system requires knowledge of the underlying genetic regulatory network that operates during an uninhibited antiviral response. In order to isolate and identify this network, we studied DCs infected with Newcastle Disease Virus (NDV), which is able to stimulate innate immunity and DC maturation through activation of RIG-I signaling, but lacks the ability to evade the human interferon response. To analyze this experimental model, we developed a new approach integrating genome-wide expression kinetics and time-dependent promoter analysis. We found that the genetic program underlying the antiviral cell state transition during the first 18-hours post-infection could be explained by a single regulatory network. Gene expression changes were driven by a step-wise multi-factor cascading control mechanism, where the specific transcription factors controlling expression changed over time. Within this network, most individual genes are regulated by multiple factors, indicating robustness against virus-encoded immune evasion genes. In addition to effectively recapitulating current biological knowledge, we predicted, and validated experimentally, antiviral roles for several novel transcription factors. More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell state transitions.
Publication Title
Antiviral response dictated by choreographed cascade of transcription factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1. HLE cells treated with oleic acid (OA) showed robust proliferation, whereas CAV-null HepG2 cells showed reduced proliferation and increased apoptosis. CAV-1 knockdown in HLE cells attenuated the OA-induced increase in proliferation and enhanced apoptosis. Liquid chromatography-tandem mass spectrometry analysis revealed that the levels of OA-containing ceramide, a pro-apoptotic factor, were higher in HepG2 and CAV-1-deficient HLE cells than in HLE cells, suggesting that CAV-1 inhibits apoptosis by decreasing the level of OA-containing ceramide. These results indicate that CAV-1 is important for NAFLD-HCC survival in fatty acid-rich environments and is a potential therapeutic target.
Publication Title
Role of caveolin-1 in hepatocellular carcinoma arising from non-alcoholic fatty liver disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant promoter methylation is known to be deeply involved in human gastric carcinogenesis, while association of Epstein-Barr virus (EBV) to the aberrant methylation has not been fully clarified. We analyzed promoter methylation in clinical gastric cancer cases using illumina's Infinium beadarray, and hierarchical clustering analysis classified gastric cancer into three subgroups: low and high methylation epigenotypes in EBV-negative cases, and markedly higher methylation epigenotype that was completely matched to EBV-positive cases. Three epigenotypes were characterized by three groups of genes: genes methylated specifically in the EBV-positive epigenotype (EBV(+)-markers, e.g. CXXC4, TIMP2, PLXND1), genes methylated both in EBV-positive and high epigenotypes (High-markers, e.g. COL9A2, EYA1, ZNF365), and genes methylated all in EBV-positive, high and low epigenotypes of gastric cancer (Common-markers, e.g. AMPH, SORCS3, AJAP1). Polycomb repressive complex (PRC)-target genes in ES cells were significantly enriched in High- and Common-markers (P=2x10-15 and 2x10-34, respectively), but not in EBV(+)-markers (P=0.2), suggesting a different cause for EBV(+)-marker methylation. Recombinant EBV was infected to low epigenotype gastric cancer cell, MKN7. In all the three independently established clones, DNA methylation was induced in High- and EBV(+)-markers after 18 weeks, demonstrating that EBV-positive epigenotype should involve methylation of Common-, High-, and EBV(+)-markers simultaneously. The de novo methylated genes were overlapped well among the three clones, and the methylation caused gene repression. In summary, gastric cancer was classified into three DNA methylation epigenotypes, EBV-positive gastric cancer showed markedly high methylation epigenotype expanding to non-PRC target genes, and EBV infection per se could induce the EBV-positive epigenotype.
Publication Title
Classification of Epstein-Barr virus-positive gastric cancers by definition of DNA methylation epigenotypes.
Sample Metadata Fields
Specimen part, Cell line
View Samples