Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand).
Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1α (HIF1A) and result in differential HIF1A-dependent gene expression.
No sample metadata fields
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesHypoxia inducible factor (HIF) is the major transcriptional regulator of cellular responses to hypoxia. The two principal HIF-a isoforms, HIF-1a and HIF-2a, are progressively stabilized in response to hypoxia and form heterodimers with HIF-1b to activate a broad range of transcriptional responses. Here we report on the pan-genomic distribution of isoform-specific HIF binding in response to hypoxia of varying severity and duration, and in response to genetic ablation of each HIF-a isoform. Our findings reveal that, despite an identical consensus recognition sequence in DNA, each HIF heterodimer loads progressively at a distinct repertoire of cell-type specific sites across the genome, with little evidence of redistribution under any of the conditions examined. Marked biases towards promoter proximal binding of HIF-1 and promoter distant binding of HIF-2 were observed under all conditions and were consistent in multiple cell type. The findings imply that each HIF isoform has an inherent property that determines its binding distribution across the genome, which might be exploited to therapeutically target the specific transcriptional output of each isoform independently. Overall design: RNA_seq analysis of hypoxic gene regulation in HKC8 and HepG2 cell lines and in RCC4 cell lines stably transfected with wtVHL
Hypoxia drives glucose transporter 3 expression through hypoxia-inducible transcription factor (HIF)-mediated induction of the long noncoding RNA NICI.
Specimen part, Cell line, Subject
View SamplesDiffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Treatment
View SamplesConditional ablation of Ezh2 in the neural crest lineage results in loss of the neural crest-derived mesenchymal derivatives. In this data sheet we determine gene expression analysis in Ezh2lox/lox and Wnt1Cre Ezh2lox/lox in E11.5 mouse BA1 cells.
Ezh2 is required for neural crest-derived cartilage and bone formation.
Specimen part
View SamplesIn this study we investigated the effect of normal chow (0 % cholesterol) or a semisynthetic diet (high sugar, 0.02 % cholesterol) fed to mice lacking either Mc4r, Ldlr or both and wildtype animals (total of 4 genotypes) by generating an expression profile of their livers after 6 months by RNA sequencing. Overall design: We investigated mice lacking either Mc4r, Ldlr or both and wildtype animals fed with normal chow or a semisynthetic diet with 10 replicates for each of the 8 resulting groups (4 genotypes * 2 diets).
Severe Atherosclerosis and Hypercholesterolemia in Mice Lacking Both the Melanocortin Type 4 Receptor and Low Density Lipoprotein Receptor.
Age, Specimen part, Cell line, Subject
View SamplesInterference with chemoresistance to enhance the efficacy of chemotherapeutics may be of great utility for cancer therapy. We have identified KINK-1 (Kinase Inhibitor of NF-kappaB-1), a highly selective small-molecule IKKkappa inhibitor, as a potent suppressor of both constitutive and induced NF-kappaB activity in melanoma cells. While KINK-1 profoundly diminished various NF-kappaB-dependent gene products regulating proliferation, cytokine production or anti-apoptotic responses, the compound by itself showed little antiproliferative or pro-apoptotic activity on the cellular level. However, its combination with some cytostatics markedly enhanced their antitumoral activities in vitro, and doxorubicin-induced NF-kappaB activation, a mechanism implicated in chemoresistance, was abrogated by KINK-1. In addition, when KINK-1 was combined with doxorubicin in an in vivo melanoma model, experimental metastasis was significantly diminished as compared to either treatment alone. Induction of chemoresistance by KINK-1 in vivo was not observed. Thus, KINK-1 or related substances might increase the susceptibility of tumors to chemotherapy.
KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment.
No sample metadata fields
View SamplesNaive spleens as well as naive and LPS-treated dendritic cells from wildtype and GPR34-/- mice were sequenced to integrate expression profiles with protein interaction networks and find functional modules that are affected by GPR34 Overall design: Expression profiles of dendritic cells and whole spleens were generated using Illumina HiSeq 2500/ Illumina HiScan
Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesAnalysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
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