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GSE27241
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T helper lymphocytes that express interleukin-17 (Th17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in Th17 cell differentiation and function with susceptibility to Crohns disease, rheumatoid arthritis, and psoriasis1-3. Thus, the pathway towards differentiation of Th17 cells and, perhaps, of related innate lymphoid cells with similar effector functions4, 5, is an attractive target for therapeutic applications. Mouse and human Th17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORt, which is required for induction of IL-17 transcription and for the manifestation of Th17-dependent autoimmune disease in mice6. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORt transcriptional activity. Digoxin inhibited murine Th17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives, 20,22-dihydrodigoxin-21,23-diol (Dig(dhd)) and digoxin-21-salicylidene (Dig(sal)), specifically inhibited induction of IL-17 in human CD4+ T cells. Using these small molecule compounds, we demonstrated that RORt is imporant for the maintenance of IL-17 expression in mouse and human effector T cells. These data suggest that derivatives of digoxin can be used as chemical probes for development of RORt-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
Publication Title
Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon- plays a crucial role in premature vascular damage in SLE. IFN- alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN- promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1 and , IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1 promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-.
Publication Title
The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon- plays a crucial role in premature vascular damage in SLE. IFN- alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN- promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1 and , IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1 promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-.
Publication Title
The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon- plays a crucial role in premature vascular damage in SLE. IFN- alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN- promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1 and , IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1 promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-.
Publication Title
The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon- plays a crucial role in premature vascular damage in SLE. IFN- alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN- promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1 and , IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1 promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-.
Publication Title
The detrimental effects of IFN-α on vasculogenesis in lupus are mediated by repression of IL-1 pathways: potential role in atherogenesis and renal vascular rarefaction.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 41 Downloadable Samples
Illumina HiSeq 2500
Description
We compare the CD4+ T cell transcriptome between obese and normal-weight children with asthma to identify molecules/pathways differentially expressed in obese asthmatic CD4+ T cells Overall design: CD4+ T cell transcriptome generated using Directional RNA-Seq library preparatio; A=Normal-weight, B=obese
Publication Title
CDC42-related genes are upregulated in helper T cells from obese asthmatic children.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Race, Subject
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Sequencing libraries were generated from total RNA samples following the mRNAseq protocol for the generation of single end (16-36 hpf, 5 day larvae, adult head and adult tail) or paired end (24 hpf) libraries (Illumina). Single end reads of 36 nucleotides and paired end reads (2 x 76 nucleotides) were obtained with a GAIIx (Illumina). Gene expression at the different stages/tissu was assessed by cufflinks and HTseq. Overall design: RNAseq on 5 differents samples: 24hpf embryos, pool of 16 hour to 36 hour embryos, 5 days old larvea, adult head and adult tail
Publication Title
Genome-wide, whole mount in situ analysis of transcriptional regulators in zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glomerular diseases account for the majority of cases with chronic renal failure. Several genes have been identified with key relevance for glomerular function. Quite a few of these genes show a specific or preferential mRNA expression in the renal glomerulus. To identify additional candidate genes involved in glomerular function in humans we generated a human renal glomerulus-specific transcript dataset (GTD) by comparing gene expression profiles from human glomeruli and tubulointerstitium obtained from six transplant living donors using Affymetrix HG-U133A arrays. This analysis resulted in 677 genes with prominent overrepresentation in the glomerulus. Genes with a priori established known prominent glomerular expression served for validation and were all found in the novel expression library (e.g. CDKN1, DAG1, DDN, EHD3, MYH9, NES, NPHS1, NPHS2, PDPN, PLA2R1, PLCE1, PODXL, PTPRO, SYNPO, TCF21, TJP1, WT1). The mRNA expression for several novel glomerulus-enriched genes identified in REGGEL was validated by qRT-PCR. Gene ontology and pathway analysis identified biological processes previously not reported to be of relevance in glomeruli including among others axon guidance. This finding was further validated by assessing the expression of the axon guidance molecules neuritin (NRN1) and roundabout receptor ROBO1 and -2. Glomerular disease associated differential mRNA regulation of ROBO2 was found in diabetic nephropathy.
Publication Title
Systematic analysis of a novel human renal glomerulus-enriched gene expression dataset.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 220 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defining cell-type specificity at the transcriptional level in human disease.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify genes with cell-lineage-specific expression not accessible by experimental micro-dissection, we developed a genome-scale iterative method, in-silico nano-dissection, which leverages high-throughput functional-genomics data from tissue homogenates using a machine-learning framework.
Publication Title
Defining cell-type specificity at the transcriptional level in human disease.
Sample Metadata Fields
Specimen part, Disease
View Samples