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GSE10463
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compounds ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo.
Publication Title
Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
RNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing Overall design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.
Publication Title
Extensive editing of cellular and viral double-stranded RNA structures accounts for innate immunity suppression and the proviral activity of ADAR1p150.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: Quiescence is a state of reversible cell cycle exit. Levels of polyadenylation factors decreases when proliferating cells become quiescent. The goals of this study are to determine the differential use of polyadenylation sites (changes in alternative polyadenylation) in quiescent vs. proliferating cells and also upon knockdown of polyadenylation factors. Methods: Two biological replicates of human dermal fibroblasts (12-1 and 12-3) were used for polyadeylation-site enriched RNA-seq on an Illumina HiSeq 2500 to compare quiescent vs. proliferating cells and polyadenylation factor knockdown vs. control cells. The reads were aligned to the human genome (hg19) uisng Tophat (2.0.14). The resulting bam files were used as an input to a python script provided by Gruber et al. (PMID: 27382025) to determine the counts for each polyadenylation site. Results: We observed a shift toward greater use of distal polyadenylation sites when the fibroblasts entered quiescence. We observed significant overlap between the genes that shift to greater distal site use with quiescence and CstF-64 or CPSF73 knockdown. Conclusions: The shift to greater distal site use with quiescence may reflect in part the reduced levels of cleavage and polyadenylation factors. Overall design: Perform polyadenylation site-enriched RNA-Seq on: (1) two biological replicates of proliferating and quiescent (contact-inhibited) cells, and (2) two biological replicates of control and polyadenylation factor (CstF64, CPSF73 or CFIm25) knockdown cells.
Publication Title
Alternative polyadenylation factors link cell cycle to migration.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Identify shear and side-specific miRNAs in Human Aortic Valvular Endothelial Cells using the following conditions: 1) fHAVEC exposed to OS (FO), 2) vHAVEC exposed to OS (VO), 3) fHAVEC exposed to LS (FL), and 4) vHAVEC exposed to LS (VL).
Publication Title
Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina HiSeq 2500
Description
Background: Although chamber specialization is critical for proper cardiac function, a comprehensive, genome-wide analysis of the cardiac transcriptome, including identification of regional differences in mRNA and lncRNA expression patterns for the four chambers and interventricular septum of the non-failing human heart, has not been performed. Methods and Results: mRNA and long noncoding RNA (lncRNA) transcriptional profiling of the left (LA) and right (RA) atria, left (LV) and right (RV) ventricles, and the interventricular septum (IVS) of non-failing human hearts (N=8) was performed by deep sequencing. Analysis of the mRNA and lncRNA expression profiles revealed that the different regions of the heart are distinct. Differential expression analysis of paired tissue samples identified 5,747 mRNAs and 2,794 lncRNAs with chamber-enriched expression patterns. The largest differences in mRNA and lncRNA expression were evident between atria and ventricular samples, including regional differences in ~20% of all cardiac expressed mRNA and lncRNA transcripts. Regional differences in mRNA and lncRNA expression were also evident, although to a lesser extent, between the LA and RA, and between the LV, RV and IVS. Gene ontology classification of differentially expressed gene sets revealed regional differences in chamber specialization, including differences in signaling, metabolism, and muscle contraction. Sex differences in mRNA and lncRNA gene expression profiles were also identified between male and female LA and RA samples. Conclusions: There are marked regional differences in the mRNA and lncRNA expression profiles in non-failing adult human heart, and are associated with chamber specialization. Overall design: 8 human hearts, 5 chambers from each
Publication Title
Regional Differences in mRNA and lncRNA Expression Profiles in Non-Failing Human Atria and Ventricles.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
A molecular and bioinformatic pipeline permitting comprehensive analysis and quantification of myocardial miRNA and mRNA expression with next-generation sequencing was developed and the impact of enhanced PI3Kalpha signaling on the myocardial transcriptome signature of pressure overload-induced pathological hypertrophy was explored. Overall design: miRNA and mRNA-Seq were carried out in four groups of mouse LV samples: WT sham, WT+TAC, caPI3Kalpha sham, caPI3Kalpha+TAC
Publication Title
Combined deep microRNA and mRNA sequencing identifies protective transcriptomal signature of enhanced PI3Kα signaling in cardiac hypertrophy.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Our strategy was to manipulate mTOR signaling in vivo, then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the non-proliferative growth model of refeeding after a period of fasting, and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from pre-term fetal rats (embryonic day 19-20) in which fetal hepatocytes are asynchronously proliferating. All three models employed rapamycin to inhibit mTOR signaling.
Publication Title
Profiling of the fetal and adult rat liver transcriptome and translatome reveals discordant regulation by the mechanistic target of rapamycin (mTOR).
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Follicular lymphoma (FL) is an indolent lymphoma associated with follicular center B cells, and typically contains the Bcl-2 chromosomal translocation t(14;18), which leads to overexpression of the anti-apoptotic intracellular protein Bcl-2. FLs are sensitive to chemotherapy; however, patient relapses occur and response duration becomes progressively shorter, with the majority of patients eventually dying from the disease. Enzastaurin (LY317615), an acyclic bisindolylmaleimide, was initially developed as an ATP-competitive selective inhibitor of PKC. We found, in agreement with recent reports, that enzastaurin inhibits cell proliferation and induces apoptosis. These results are consistent with decreased phosphorylation of the Akt pathway and its downstream targets. To provide new insights into the anti-tumor action of enzastaurin on non-Hodgkin lymphoma, we investigated its effects on gene expression profiles of the B cell lymphoma RL cell line by oligonucleotide microarray analysis. We identified a set of 41 differentially expressed genes, mainly involved in cellular adhesion, apoptosis, inflammation, and immune and defense responses. These observations provide new insights into the mechanisms involved in the induction of apoptosis by enzastaurin in B cell lymphoma cell lines, and identify possible pathways that may contribute to the induction of apoptosis.
Publication Title
Genomic profiling of enzastaurin-treated B cell lymphoma RL cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 256 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 159 Downloadable Samples
- Ion Torrent Proton
Description
Cardiovascular disease is the major cause of morbidity and death in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Patients with CKD and ESRD are at high risk for myocardial dysfunction, ischemia and heart failure. The mechanisms linking impaired renal function and increased risk for cardiovascular diseases, however, remain elusive. In addition, conventional therapeutics proven effective in reducing cardiovascular events in general population fail to provide similar benefits in uremic patients. There is a clear need to identify novel mediators of cardiovascular complications in uremic patients to provide insights into the pathogenesis, to tailor clinical care based on cardiovascular risks, and to develop new therapeutic strategies. It has become increasingly clear that the transcription of the eukaryotic genome is far more pervasive and complex than previously appreciated. While the expression of messenger RNAs (mRNAs) and microRNAs (miRNAs) account for only ~1% of all transcribed species, up to 90% of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs), a heterogeneous group of non-coding transcripts longer than 200 nucleotides. LncRNAs have been shown to be functional and involved in specific physiological and pathological processes through epigenetic, transcriptional and post-transcriptional mechanisms. While the roles of lncRNAs in human diseases including cancer and neurodegenerative disorders are beginning to emerge, it remains unclear how lncRNA regulation contributes to cardiovascular complications in patients with renal dysfunction. In this proposal, we seek to apply next-generation sequencing technology to investigate circulating (plasma) lncRNA expression in control subjects and in patients with CKD and ESRD. We will test the hypothesis that circulating lncRNA expression signature can reflect the underlying kidney disease states in patients with CKD and ESRD. In addition, we will determine if circulating lncRNA expression signature could be a sensitive and specific biomarker to predict adverse cardiovascular events in patients with ESRD. Overall design: During the initial exploratory phase, plasma total RNA was isolated from 48 study subjects (28 ESRD, 8 CKD and 12 controls), followed by amplicon-based RNA sequencing (AmpliSeq TranscriptomeTM, Thermo Fisher), which allows simultaneous quantification of 20812 human transcripts, including 2228 lncRNAs. Differential expression analyses following RNASeq identified lncRNAs that were altered with ESRD, compared to control/CKD, as well as lncRNAs that were linked to adverse CV outcomes in uremic patients. The prognostic role of plasma lncRNAs in patients with ESRD were then validated in an independent cohort of 111 subjects.
Publication Title
Circulating long noncoding RNA DKFZP434I0714 predicts adverse cardiovascular outcomes in patients with end-stage renal disease.
Sample Metadata Fields
Subject
View Samples