We identified Ncoa3 as a regulator of neuronal morphology and microRNA activity. In order to uncover target genes of this transcriptional coactivator we performed this microarray analysis.
A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function.
Specimen part, Treatment
View SamplesFamilial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. In order to advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells (PBMCs) from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with 2.5-fold difference in expression (P = 0.05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, pro-apoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of IL-6, IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of anti-apoptotic proteins were overexpressed in patients with FHL. This, first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underly the immunobiology of FHL.
Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis.
Specimen part
View SamplesThe proper mammalian oocytes maturation is recognized as reaching MII stage and accumulation of mRNA and proteins in cell cytoplasm following fertilization. The proper course of folliculogenesis and oogenesis is orchestrated with morphogenesis significantly influencing further zygote formation and embryos growth. This study was aimed to determinate new transcriptomic markers of porcine oocytes morphogenesis associated with cell maturation capacity.
"Cell Migration" Is the Ontology Group Differentially Expressed in Porcine Oocytes Before and After In Vitro Maturation: A Microarray Approach.
Specimen part
View SamplesPreterm birth is an important unsolved clinical problem. Despite advanced treatments, infants who survive prematurity remain at increased risk for permanent disabilities. In approximately one-third of cases, prematurity is related to infection and/or inflammation, which renders hostile the normally receptive intrauterine environment. Proinflammatory cytokines provoke up-regulation of genes that promote uterine contractions. Using monolayer cultures of human cervical fibroblast cells as a model, we profiled the global pattern of gene expression in response to cytokine challenge.
Progesterone Receptor Signaling Selectively Modulates Cytokine-Induced Global Gene Expression in Human Cervical Stromal Cells.
Treatment
View SamplesThe objective was to study the transcriptomic changes in adipose tissue in the early stages of lactation, specifically in Bos Taurus, Holstein dairy cattle as a function of milk production and genetic merit.
Differential expression of genes in adipose tissue of first-lactation dairy cattle.
Specimen part
View SamplesHuman Burkitt's lymphoma ST486 cells were transduced with non-target control shRNA lentiviral vectors, FOXM1 shRNA, and MYB shRNA lentiviral vectors. Total RNA was isolated 24h later. cRNA was produced with the standard one-step IVT protocol (Affymetix) and hybridized in U95Av2 gene chips (Affymetrix).
Correlating measurements across samples improves accuracy of large-scale expression profile experiments.
Cell line, Time
View SamplesBranching morphogenesis in lung development is regulate by growth factor signaling. Wnt signaling is one of the important singnaling pathway that is required for progenitor maintainance. In the presence of CHIR99021, an agonist for the beta-catenin pathway of Wnt signaling, specific group of genes are upregulated in cultured lung epithelium.
Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.
Specimen part
View SamplesChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T-cells, followed by extensive biochemical validation, reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind to several thousands target gene promoters, up to an order of magnitude increase over conventional analysis methods. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and regulation. Finally, the increased sensitivity reveals a combinatorial regulatory program in which MYC co-binds to virtually all NOTCH1-bound promoters. Overall, these results suggest an unappreciated complexity of transcriptional regulatory networks and highlight the fundamental importance of genome-scale analysis to represent transcriptional programs.
ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes.
No sample metadata fields
View SamplesAlveolar macrophages are the first line of defense against pathogens in the lungs of all mammalian species and therefore may constitute an appropriate therapeutic target cell in the treatment and prevention of opportunistic airway infections. Analysis of alveolar macrophages from several species has revealed a unique cellular phenotype and transcriptome, presumably linked to their distinct airway environment and function in host defense. The current study extends these findings to the horse.
Comparative transcriptome analysis of equine alveolar macrophages.
Treatment
View SamplesToxoplasma gondii is a ubiquitous apicomplexan parasite of mammals and birds and an important pathogen of humans. IFN-g is the major mediator of host resistance against T. gondii but intriguingly, parasite-infected host cells including macrophages are severely impaired to respond to IFN-g due to defective transcriptional activation of target genes. Here, we tested the possibility that the impaired responsiveness of T. gondii-infected macrophages to IFN-g can be restored by inhibiting histone deacetylases (HDACs) using the class I-specific inhibitor MS-275. Treatment of RAW264.7 cells with MS-275 indeed increased MHC class II surface expression in infected and non-infected cells and largely abolished the inhibition of IFN-g-regulated MHC class II expression exerted by T. gondii. Genome-wide transcriptome profiling revealed that MS-275 increased mean mRNA levels of IFN-g-regulated genes particularly in non-infected macrophages. Transcript levels of 33% of IFN-g secondary response genes but only those of a few primary response genes were also increased by MS-275 in T. gondii-infected cells. Importantly, the unresponsiveness of parasite-infected cells to IFN-g was however not abolished by MS-275. Furthermore, MS-275 also up-regulated several anti-inflammatory cytokines or signaling molecules in T. gondii-infected macrophages. It additionally regulated expression of more than 2500 genes in non-infected macrophages expression of which was surprisingly counteracted by prior infection with T. gondii. FACS analysis and immunofluorescence microscopy revealed that MS-275 did not considerably diminish the number of parasite-positive cells or the intracellular replication in macrophages stimulated or not with IFN-g. Thus, a supportive therapy using MS-275 appears inappropriate for treatment of toxoplasmosis. Overall design: High throughput RNA profiles from IFN-g-activated monocytic cells infected with Toxoplasma gondii and treated with MS-275 and control cells were generated by Illumina sequencing. Five experimental conditions with 2 biological replicates each were analysed.
Histone deacetylase inhibitor MS-275 augments expression of a subset of IFN-γ-regulated genes in Toxoplasma gondii-infected macrophages but does not improve parasite control.
Subject
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