Low-level infection is believed to play a role in the degradation of the outer blood retinal barrier, which is composed of retinal pigment epithelial (RPE) cells.
Microarray analysis of gene expression in West Nile virus-infected human retinal pigment epithelium.
Sex, Specimen part, Disease, Disease stage, Cell line
View SamplesIt has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis. Overall design: Transcriptomic profiles were obtained from palmoplantar (n = 3), scalp (n = 8), and conventional psoriatic skin (n = 8) as well as healthy control skin (n = 9) biopsies on the Illumina HiSeq 2000/4000 platforms. Multi-parameter FACS was also performed on each biopsy sample to obtain T cell populations (CD4+ T effectors, CD8+ T cells, and CD4+Foxp3+ Tregs).
RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.
Specimen part, Disease, Disease stage, Subject
View SamplesHuntington's disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Transcriptional profiling of muscle in treated and untreated wild-type and R6/2 mice was performed to analyze the effect of the ActRIIB decoy on genes and pathways involved in maintaining normal muscle physiology as well as those dysregulated due to the mutant HTT gene mutation. Overall design: RNAseq was performed on tibialis muscle from wild-type, wildtype + decoy, R6/2 and R6/2 + decoy; N = 10 per group. RNAseq was done on an Illumina Hi-seq 2000. Paired-end sequencing was obtained, 4-plexed across lanes for a minimum of 38 million 50mer paired reads per sample
Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington's disease mice.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesHuntington’s disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models and PDE10 loss may represent a homeostatic adaptation to maintain signaling. Elevation of both cAMP and cGMP by PDE10 inhibition were required for rescue. Phosphoproteomic profiling of striatum in response to PDE10 inhibition highlighted plausible neural substrates responsible for the improvement. Early chronic PDE10 inhibition in Q175 mice showed improvements beyond those seen with acute administration after symptom onset, including partial reversal of striatal deregulated transcripts and the prevention of the emergence of HD neurophysiological deficits. Overall design: Transcriptional profiling of cortex and striatal tissue following chronic dosing of either vehicle or the PDE10A inhibitor PF-02545920 (0.32, 1 and 3.2 mg/kg po qd) in the Q175 homozygous knock-in mouse model of Huntington’s disease (dosing from 5-weeks to 9 months of age).
Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington's Disease Models.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesHsp90 is critical for regulation of the phenotype and functional activity of human T lymphocytes and natural killer (NK) cells.
Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells.
Specimen part, Treatment
View SamplesThe host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of numerous diseases associated with exacerbated inflammation. Here, we identify Topoisomerase 1 (Top1) as a critical positive regulator of RNA polymerase II (RNAPII) transcriptional activity at pathogen-induced genes. Notably, depletion or chemical inhibition of Top1 suppresses the host response against replicating Influenza and Ebola viruses as well as bacterial products. As a result, therapeutic pharmacological inhibition of Top1 protects mice from death in experimental models of chemical- and pathogen-induced lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life threatening infections characterized by an acutely exacerbated immune response. Overall design: RNA seq was performed on Ebola (Wild type and mutant) infected or uninfected THP-1 cells in the presence of DMSO or Camptothecin
Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.
Specimen part, Treatment, Subject
View SamplesThese data are from the brains (amygdala and hippocampus) of mice originally derived from a cross between C57BL/6J and A/J inbred strains. We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning, which is a measure of fear learning. We selected for a total of 4 generations. Fear learning differed in the selected lines and this difference was stronger with each successive generation of selection. We identified several QTLs for the selection response, including a highly significant QTL at the tyr locus (p < 9.6(-10)). We used Affymetrix microarrays to identify many differentially expressed genes in the amygdala and hippocampus of mice from the final generation of selection. Amygdala and hippocampus samples were rapidly dissected out of experimentally nave mice from each selected line. Three samples were pooled and hybridized to each array. Experimentally nave mice were used because the behavior of the mice can be reliably a nticipated due to their lineage. Thus these gene expression differences are not due to the response to human handling, foot shock or fear-inducing conditioned stimuli. We have a second similar study that focuses on a different selected population that was based on C57BL/6J and DBA/2J mice (see GES4035).
Rapid selection response for contextual fear conditioning in a cross between C57BL/6J and A/J: behavioral, QTL and gene expression analysis.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells.
Specimen part
View SamplesPrevious results from a genome scan in a F2 Iberian by Meishan intercross showed several chromosome regions associated with litter size traits. In order to identify candidate genes underlying these QTL we have performed an ovary gene expression analysis during pregnancy. F2 sows were ranked by their estimated breeding values for prolificacy, the six sows with higher EBV (HIGH prolificacy) and the six with lower EBV (LOW prolificacy) were selected. Samples were hybridized to Affymetrix porcine expression microarrays. The statistical analysis with a mixed-model approach identified 221 differentially expressed probes, representing 189 genes. These genes were functionally annotated in order to identify the genetic pathways overrepresented. Among the most represented functional groups the first one was immune system response activation against external stimulus. The second group was made up of genes which regulate the maternal homeostasis by complement and coagulation cascades. The last group was involved on lipid and fatty acid enzymes of metabolic processes, which participate in steroidogenesis pathway. In order to identify powerful candidate genes for prolificacy, the second approach of this study was merging microarray data with position information of QTL affecting litter size, previously detected in the same experimental cross. According to this, we have identified 27 differentially expressed genes co-localized with QTL for litter size traits, which fulfill the biological, positional and functional criteria.
Differential gene expression in ovaries of pregnant pigs with high and low prolificacy levels and identification of candidate genes for litter size.
Specimen part
View SamplesAssessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important, given that such differences may impact their potential therapeutic use.
The quantitative proteomes of human-induced pluripotent stem cells and embryonic stem cells.
Specimen part
View Samples