Analysis of global gene expression profiles of flow cytometry-sorted, different pathogen-specific CD4+ T cell populations from the same peripheral blood mononuclear cells (PBMC), to identify molecular parameters that regulate differential susceptibilities of these CD4+ T cells to HIV infection. The results reveal distinct gene expression profiles between CMV-specific and tetanus toxoid/Candida-specific CD4+ T cells that involved selective upregulation of comprehensive innate antiviral
Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection.
Specimen part
View SamplesAnalysis of global gene expression profiles of FACS-sorted, human Ad5- and CMV-specific CD4 T cells from the same PBMC sample of healthy donros, using affymetrix Human Gene 2.0ST Gene-Chips;
Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals.
Specimen part, Subject
View SamplesNumerous mammalian proto-oncogene and other growth-regulatory transcripts are upregulated in malignancy due to abnormal mRNA stabilization. In hepatoma cells expressing a hepatitis C virus (HCV) subgenomic replicon, we found that the viral nonstructural protein 5A (NS5A), a protein known to bind to viral RNA, also bound specifically to human cellular transcripts that encode regulators of cell growth and apoptosis, and this binding correlated with transcript stabilization. An important subset of human NS5A-target transcripts contained GU-rich elements, sequences known to destabilize mRNA. We found that NS5A bound to GU-rich elements in vitro and in cells. Mutation of the NS5A zinc finger abrogated its GU-rich element-binding and mRNA stabilizing activities. Overall, we identified a molecular mechanism whereby HCV manipulates host gene expression by stabilizing host transcripts in a manner that would promote growth and prevent death of virus-infected cells, allowing the virus to establish chronic infection and lead to the development of hepatocellular carcinoma. Overall design: Calculate mRNA decay rate by examining RNA-seq expression levels of 2 samples (Huh and Huh-HCV) at 3 time points (0h, 3h, and 6h) after transcription arrest. RNA-IP followed by RNA-seq on 2 samples (Huh and Huh-HCV).
The hepatitis C viral nonstructural protein 5A stabilizes growth-regulatory human transcripts.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The genomic response to retinal disease and injury: evidence for endothelin signaling from photoreceptors to glia.
No sample metadata fields
View SamplesThis experiment was designed to identify transcripts that exhibit changes in abundance in the context of retinal degeneration by comparing transcript levels in adult wild type and prCAD -/- mouse retinas.
The genomic response to retinal disease and injury: evidence for endothelin signaling from photoreceptors to glia.
No sample metadata fields
View SamplesTranscriptional profiles were compared between dark adapted and light damaged BALBc (albino) mouse retinas.
The genomic response to retinal disease and injury: evidence for endothelin signaling from photoreceptors to glia.
No sample metadata fields
View SamplesFz4 and Fz8 cooperate in regulating the branching morhpogenesis of the developing kidney during mouse embryonic development, hence determines the eventual kidney size.
Genetic mosaic analysis reveals a major role for frizzled 4 and frizzled 8 in controlling ureteric growth in the developing kidney.
Specimen part
View SamplesRecent studies have demonstrated that upon encountering a pathogenic stimulus, robust metabolic rewiring of immune cells occurs. A switch away from oxidative phosphorylation to glycolysis, even in the presence of sufficient amounts of oxygen (akin the Warburg effect), is typically observed in activated innate and adaptive immune cells and is thought to accommodate adequate inflammatory responses. However, whether the Warburg effect is a general phenomenon applicable in human monocytes exposed to different pathogenic stimuli is unknown. Our results using human monocytes from healthy donors demonstrate that the Warburg effect only holds true for TLR4 activated cells. Although activation of other TLRs leads to an increase in glycolysis, no reduction or even an enhancement in oxidative phosphorylation is observed. Moreover, specific metabolic rewiring occurs in TLR4 vs. TLR2 stimulated cells characterized by altered gene expression profiles of pathways related to metabolism, changes in spare respiratory capacity of the cells and differential regulation of mitochondrial enzyme activity. Similarly, results from ex vivo and in vivo studies demonstrate metabolic rewiring of immune cells that is highly dependent on the type of pathogenic stimulus. Although the Warburg effect is observed in human monocytes after TLR4 activation, we propose that this typical metabolic response is not applicable to other inflammatory signalling routes including TLR2 in human monocytes. Instead, each pathogenic stimulus and subsequently activated inflammatory signalling cascade induces specific metabolic rewiring of the immune cell to accommodate an appropriate response.
Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes.
Specimen part, Treatment, Subject
View SamplesEndothelin signaling is required for neural crest migration and homeostatic regulation of blood pressure. Here we report that constitutive over-expression of Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by inhibiting endothelial cell (EC) migration across the retinal surface and subsequent EC invasion into the retina. Developing endothelial cells exist in one of two states: tip cells at the growing front, and stalk cells in the vascular plexus behind the front. This division of endothelial cell states is one of the central organizing principle of angiogenesis. In the developing retina, Edn2 over-expression leads to over-production of endothelial tip cells by both morphologic and molecular criteria. Spatially localized over-expression of Edn2 produces a correspondingly localized endothelial response. Edn2 over-expression in the early embryo inhibits vascular development at mid-gestation, but Edn2 over-expression in developing skin and brain has no discernable effect on vascular structure. Inhibition of retinal angiogenesis by Edn2 requires expression of Endothelin receptor A (Ednra) but not Ednrb in the neural retina. Taken together, these observations imply that the neural retina responds to Edn2 by synthesizing one or more factors that promote the endothelial tip cell state and inhibit angiogenesis. The response to Edn2 is sufficiently potent that it over-rides the activities of other homeostatic regulators of angiogenesis, such as vascular endothelial growth factor.
Endothelin-2 signaling in the neural retina promotes the endothelial tip cell state and inhibits angiogenesis.
Specimen part
View SamplesMucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals. To gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and tested for traits predicted by the genome using physiological experiments. Although thought to be a mucus degrader, its genome surprisingly predicts that M. schaedleri has limited capacity for degrading host-derived mucosal glycans or other complex polysaccharides. Rather, it may utilize small compounds such as peptides, amino acids, glycerol, and short chain fatty acids. Additionally, it can reduce nitrate and has systems for scavenging oxygen and reactive oxygen species, which accounts for its presence close to the mucosal tissue and during inflammation. Also of note, M. schaedleri harbors a type VI secretion system (T6SS) and several putative effector proteins containing eukaryotic domains, which suggest intimate interactions with the host and a role in inflammation. Examination of the individual phylogenies of all genes in the M. schaedleri genome revealed extensive horizontal gene transfer, primarily from intestinal Epsilon- and Deltaproteobacteria. Though M. schaedleri utilizes non-horizontally-transferred pathways (e.g. nitrate reduction), horizontally-acquired pathways from gut organisms (e.g. T6SS and glycerol-P utilization) are also likely also important for its survival in the intestine, suggesting that lateral gene transfer may have played a key role in facilitating its establishment in the gut ecosystem.
Lifestyle and Horizontal Gene Transfer-Mediated Evolution of <i>Mucispirillum schaedleri</i>, a Core Member of the Murine Gut Microbiota.
Sex, Specimen part, Treatment
View Samples