The objective of this study is to assess the effects of the Serum Response Factor deletion on the cardiac gene expression program at different time points after the deletion (day 8 and day 25) and to compare the response of SRF-deficient heart and control heart to phenylephrine, an alpha-adrenergic agonist triggering cardiac hypertrophy.
Nicotinamide Riboside Preserves Cardiac Function in a Mouse Model of Dilated Cardiomyopathy.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sex, Age, Specimen part
View SamplesIn recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. Trait-associated SNPs located in putative regulatory regions likely exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. To this end, left ventricular mycardium samples from non-diseased human donor hearts were hybridized to Illumina HumanOmniExpress BeadChips for genotyping (n = 129) and Illumina Human HT12 Version 4 BeadChips (n = 129) for transcription profiling.
Genome-wide identification of expression quantitative trait loci (eQTLs) in human heart.
Sex, Age, Specimen part
View SamplesComparison of gene expression level of 3T3-L1, PMEF and ES cell derived adipocytes to eWAT samples.
Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Specimen part, Cell line
View SamplesRAW264.7 mouse macrophages were transfected with negative control and miR-342-3p mimics and subjected to microarray analysis 18 hours after the transfection.
The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.
Specimen part, Cell line
View SamplesmRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients.
Specimen part, Cell line
View SamplesmRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Deoxyhypusine synthase (DHPS) inhibitor GC7 induces p21/Rb-mediated inhibition of tumor cell growth and DHPS expression correlates with poor prognosis in neuroblastoma patients.
Specimen part, Cell line
View SamplesGenome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Specimen part
View SamplesBackground: In human malaria, parasites of the genus Plasmodium elicit expansion of atypical memory B cells (atMBCs), which lack the classical markers CD21 and CD27. We have identified a putative population of analogous B cells in a murine model of infection with P. chabaudi, delineated by the marker FCRL5. We performed RNA-Seq on FCRL5+ and FCRL5- B cells sorted from infected mice, so as to characterize the transcriptional profile of these cells and permit comparison to atMBCs in humans. Results: FCRL5+ B cells were found to have distinct transcriptional profiles from FCRL5- B cells, with approximately 400 genes exhibiting significant differences between the two groups. Additionally, about 25% of these differentially expressed genes were also differentially expressed in human atMBCs versus classical MBCs, as previously described by Sullivan et al (PLoS Pathogens 2015). Conclusions: FCRL5+ class-switched B cells are a transcriptionally distinct subset arising in P. chabaudi infection, with transcriptional similarities to human atMBCs that develop in chronic malaria settings. Overall design: Class-switched B cells (IgM- IgD- CD19+) were isolated into FCRL5+ and FCRL5- populations by double-sorting from the blood of C57BL/6 adult female mice 21 days post-infection with Plasmodium chabaudi. Pools of ~1000 cells were isolated and processed for RNA sequencing. 5 biological replicates were analyzed for each sample type.
FCRL5<sup>+</sup> Memory B Cells Exhibit Robust Recall Responses.
Specimen part, Subject
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