The study of the mechanisms leading to cardiac hypertrophy is essential to better understand cardiac development and regeneration. Pathological conditions such as ischemia or pressure overload can induce a release of extracellular nucleotides within the heart. We recently investigated the potential role of nucleotide P2Y receptors in cardiac development. We showed that adult P2Y4-null mice displayed microcardia resulting from defective cardiac angiogenesis. Here we show that loss of another P2Y subtype called P2Y6, a UDP receptor, was associated with a macrocardia phenotype and amplified pathological cardiac hypertrophy. Cardiomyocyte proliferation and size were increased in vivo in hearts of P2Y6-null neonates, resulting in enhanced post-natal heart growth. We then observed that loss of P2Y6 receptor enhanced pathological cardiac hypertrophy induced after isoproterenol injection. We identified an inhibitory effect of UDP on in vitro isoproterenol-induced cardiomyocyte hyperplasia and hypertrophy. The present study identifies mouse P2Y6 receptor as a regulator of cardiac development and cardiomyocyte function. P2Y6 receptor could constitute a therapeutic target to regulate cardiac hypertrophy. Overall design: WT and P2Y6 KO mice aged between 8 and 12 weeks were intraperitoneally injected with 50 mg/kg/day isoproterenol or saline solution, daily during 7 days, then hearts were harvested and weighted. Ventricles were then stored for RNA extraction.
Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy.
Specimen part, Treatment, Subject
View SamplesAbstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis.
Platelets and platelet-like particles mediate intercellular RNA transfer.
Specimen part, Cell line
View SamplesThe heterogeneity of cortical dopamine D2 receptor expressing cells is not well characterized
High Sensitivity Mapping of Cortical Dopamine D2 Receptor Expressing Neurons.
Specimen part
View SamplesAccording to the Canadian Food Inspection Agency and Health Canada, genetically modified crops are considered safe if they are substantially equivalent to a conventional crop in regards to agronomic, physiological and compositional characteristics. A recurring issue in safety assessment of genetically modified crops is the paucity of analytical methods to detect unintended or unexpected outcomes of genetic modification. Traditional targeted compound comparative analyses are limited in scope and capacity to detect unintended changes in chemical composition. This study explored the potential of using microarray technology to assess the substantial equivalence of gene expression profiles between genetically modified and conventional soybean cultivars. Different pre processing methods were applied to the raw expression data from the arrays, and clustering methods were used to try and differentiate the genetically modified cultivars from the conventional cultivars. Results showed that more variation existed between different strains of conventional cultivars than between conventional and genetically modified cultivars.
Effect of transgenes on global gene expression in soybean is within the natural range of variation of conventional cultivars.
No sample metadata fields
View SamplesThe inflammatory response of preterm infants' intestine underlines its inability to respond to hemodynamic stress, microbes and nutrients. Recent evidence suggests that exogenous epidermal growth factor (EGF) exerts a therapeutic influence on neonatal enteropathies. However, the molecular mechanisms underlying the beneficial effects of EGF remain to be clarified. The purpose of this study was to evaluate the impact of EGF on the gene expression profiles of the developing human small and large intestine at mid-gestation in serum-free organ cultures using Illumina microarrays.
Anti-inflammatory effects of epidermal growth factor on the immature human intestine.
Specimen part
View SamplesWe have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternate splice site usage, intron retention), differential 5 UTR (initiation of transcription) usage, and differential 3 UTR (alternative polyadenylation) usage.
Genome-wide analysis of transcript isoform variation in humans.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor ID2 prevents E proteins from enforcing a naïve T lymphocyte gene program during NK cell development.
Specimen part
View SamplesTranscriptional profiling of small intestinal explants cultured in the absence or in the presence of Ibuprofen (100 M).
Impaired antimicrobial response and mucosal protection induced by ibuprofen in the immature human intestine.
Specimen part
View SamplesTranscriptional profiling after inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells
Transcriptional profiling in response to inhibition of cellulose synthesis by thaxtomin A and isoxaben in Arabidopsis thaliana suspension cells.
Specimen part
View SamplesDifferent inflammatory stimuli contribute to the formation of atherosclerosis. It is hypothesized that although the end result is the same - plaque formation in arterial vessels - the pathogenesis is dependent on the etiology. In particular, platelets will respond differently depending on the inflammatory stimuli and timepoint.
Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans.
Specimen part, Treatment, Time
View Samples