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GSE2116
Rattus norvegicus
23 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
Left ventricular gene expression profiles from 12-, 16- and 20-months old spontaneously hypertensive rats (SHRs) were compared with left ventricular profiles seen in age-matched Wistar-Kyoto (WKY) rats by screening Affymetrix U34A arrays (there are 4 samples in each timepoint except 3 samples of 20-months old WKYs).
Publication Title
Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38 in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart.
Publication Title
Identification of cell cycle regulatory and inflammatory genes as predominant targets of p38 mitogen-activated protein kinase in the heart.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The objective of the study was to find cardiac GATA-4 target genes by overexpressing GATA-4 transcription factor in the left ventricle by adenoviral gene transfer.
Publication Title
GATA-4 is an angiogenic survival factor of the infarcted heart.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
The transcriptional profile of A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs) Overall design: A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs)
Publication Title
Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
The transcriptional profile of A673 parental, and SP-2509 drug resistant washout cells (4 and 6 months) Overall design: Following generation of A673 SP-2509 drug resistant cells (chronic exposure for 7 months), drug was withdrawn with cell pellets collected 4 and 6 months after removal.
Publication Title
Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation.
Sample Metadata Fields
Disease, Treatment, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential Argonaute iCLIP, mRNA quantification with RNA-Seq, and 3'UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3'UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation reminiscent of sequence-specific transcription factors. Our study provides comprehensive maps of miR-155 regulatory RNA networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key cell types of the adaptive and innate immune systems. Overall design: Primary dendritic cells, B cells, CD4 T cells, and macrophages from C57BL/6J wild type and miR-155 KO mice were cultured in RPMI medium with 10% FBS. Prior to harvesting primary dendritic cells, mice were subcutaneously injected with one million B16 melanoma cells expressing Flt3 ligand for about two weeks. After purification of splenic CD11c+ dendritic cells by CD11c microbeads (Miltenyi Biotec), dendritic cells were activated in a medium containing 100 ng/ml LPS (SIGMA) and 20 ng/ml GMSCF (Tonbo). Splenic primary B cells were purified by negative selection using Dynabeads Mouse CD43 (Invitrogen), and activated in a medium containing 25 ug/ml LPS and 6.5 ng/ml mIL4 (PeproTech). CD4 T cells from lymph node and spleen were purified with Dynabeads FlowComp Kit (Invitrogen). CD4+CD25-CD44- T cells were then activated with Dynabeads Mouse T-Activator CD3/CD28 (Invitrogen). Intraperitoneal macrophages, induced by thioglycollate injection, were harvested and activated with 100 ng/ml LPS.
Publication Title
The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential Argonaute iCLIP, mRNA quantification with RNA-Seq, and 3'UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3'UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation reminiscent of sequence-specific transcription factors. Our study provides comprehensive maps of miR-155 regulatory RNA networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key cell types of the adaptive and innate immune systems. Overall design: Primary dendritic cells, B cells, CD4 T cells, and macrophages from C57BL/6J wild type and miR-155 KO mice were cultured in RPMI medium with 10% FBS. Prior to harvesting primary dendritic cells, mice were subcutaneously injected with one million B16 melanoma cells expressing Flt3 ligand for about two weeks. After purification of splenic CD11c+ dendritic cells by CD11c microbeads (Miltenyi Biotec), dendritic cells were activated in a medium containing 100 ng/ml LPS (SIGMA) and 20 ng/ml GMSCF (Tonbo). Splenic primary B cells were purified by negative selection using Dynabeads Mouse CD43 (Invitrogen), and activated in a medium containing 25 ug/ml LPS and 6.5 ng/ml mIL4 (PeproTech). CD4 T cells from lymph node and spleen were purified with Dynabeads FlowComp Kit (Invitrogen). CD4+CD25-CD44- T cells were then activated with Dynabeads Mouse T-Activator CD3/CD28 (Invitrogen). Intraperitoneal macrophages, induced by thioglycollate injection, were harvested and activated with 100 ng/ml LPS. Each condition has 3 sequencing replicates.
Publication Title
The effect of cellular context on miR-155-mediated gene regulation in four major immune cell types.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
We undertook an integrative technological approach to compare miRNA detection capability of three high-throughput commercial platforms. Overall design: We artificially introduced human precursor, 2’-O-methyl modified and mature spiked-in miRNAs in a controlled fashion into native human placenta total RNA.
Publication Title
Differences in microRNA detection levels are technology and sequence dependent.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Flaviviruses, particularly Japanese encephalitis virus (JEV) and West Nile virus (WNV), are important causes of virus-induced central nervous system (CNS) disease in humans. We used microarray analysis to identify cellular genes that are differentially regulated following infection of the brain with JEV (P3) or WNV (New York 99). Gene expression data for these flaviviruses was compared to that induced following infection of the brain with reovirus (Type 3 Dearing), an unrelated neurotropic virus. Although several studies have described gene expression changes following virus infection of the brain, this report is the first to directly compare large-scale gene expression data from different viruses. We found that a large number of genes were up-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001), including genes associated with interferon signaling, the immune system, inflammation and cell death/survival signaling. In addition, genes associated with glutamate signaling were down-regulated in common to infections with all 3 viruses (fold change > 2, P < 0.001). These genes may serve broad spectrum therapeutic targets for virus-induced CNS disease. A distinct set of genes were up-regulated following flavivirus-infection, but not following infection with reovirus. These genes were associated with tRNA charging and may serve as therapeutic targets for flavivirus-induce CNS disease.
Publication Title
Virus-induced transcriptional changes in the brain include the differential expression of genes associated with interferon, apoptosis, interleukin 17 receptor A, and glutamate signaling as well as flavivirus-specific upregulation of tRNA synthetases.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
We examined the effects of TNFa and Spt5, the major DSIF subunit, on nascent and mature transcripts using RNA-Seq of chromatin-associated and cytoplasmic transcripts. Overall design: RNA was extracted from the cytosolic and chromatin fractions of control and Spt5 KD cells that were treated with TNFa for 1 hour
Publication Title
Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5.
Sample Metadata Fields
No sample metadata fields
View Samples