To assess the nature of CD8+CD40L+ memory Tcells, we compared the gene expression to CD8+CD40L- and CD4+ counterparts, and found similarities in expression of genes encoding cytokines
CD40L expression permits CD8+ T cells to execute immunologic helper functions.
Sex, Specimen part
View Sampleswe used technique that allows the molecular characterization of particular neuronal subpopulations based on their neuroanatomical projections and the locations of their cell bodies. This 'retro-TRAP' (translating ribosome affinity purification from retrogradely labeled neurons) approach relies on viral injection into an anatomical area targeted by the neurons of interest, followed by selective precipitation of ribosomes from retrogradely labeled cell bodies, and subsequent RNAseq analysis. Overall design: By comparing the mRNAs enriched in the NGC neurons which are retrogradely labeled due to viral injection into central thalamus, to gene expression of non-labeled surrounding cells in NGC, and then performing a comprehensive bioinformatics analysis of these results, we were able to identify genes enriched in these cells. This procedure allowed us to highlight genes and pathways unique to these neurons with projections ascending to thalamus, as compared to other cells in reticular NucleusGigantocellularis.
Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal.
Sex, Specimen part, Cell line, Subject
View SamplesEbf genes regulate differentiation of several cell type. Ebf2 is expressed in Schwann cells and Ebf2-/- mice show among other phenotypical abnormalities a delay in the onset of myelination associated to a decreased expression of genes regulating myelination. In addition at one month of age Ebf2-/- mice show decreased motor conduction velocity and morphological alteration in sciatic nerves. Ebf2 target genes are unknown. To identify Ebf2 target genes with a role in myelination, we compared the expression profiles of sciatic nerves isolated from P2 Wt and Ebf2-/- mice by microarray analysis.
The Transcription Factors EBF1 and EBF2 Are Positive Regulators of Myelination in Schwann Cells.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
No sample metadata fields
View SamplesWhen C. elegans larvae hatch in the absence of food they persist in a stress resistant, developmentally arrested state (L1 arrest). We characterized mRNA expression genome-wide in a pair of bifurcating time series starting in the late embryo and proceeding through the hatch in the presence and absence of food (E. coli).
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
No sample metadata fields
View SamplesMurine B cells can be activated via the surface receptors TLR4 and CD40. For a global assessment of differences in gene expression between these two different modes of B cell activation a genome wide transcriptome analysis was performed. In order to dissect different gene expression profiles of B cells, activation was induced by LPS or LPS + anti-CD40 for 24h and 72h. Both activation states were compared to each other but also to nave B cells.
IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases.
Sex, Specimen part
View SamplesThe goal of this study was to identify the molecular characteristics and putative markers distinguishing IL-10eGFP+CD138hi and IL-10eGFP-CD138hi plasmocytes. To this end, IL-10eGFP B-green mice were challenged intravenously with Salmonella typhimurium (strain SL7207, 10e7 CFU), and IL-10eGFP+CD138hi as well as IL-10eGFP-CD138hi plasmocytes were isolated from the spleen on the next day. For this, single cell suspensions were prepared, cells were treated with Fc block (10 g/ml, anti-CD16/CD32, clone 2.4G2), and then stained with an antibody against CD138 conjugated to PE (1/400; from BD Pharmingen) followed by incubation with anti-PE microbeads (Miltenyi Biotech). CD138+ cells were then enriched on Automacs (Miltenyi Biotech) using the program possel_d2. Cells were then stained with anti-CD19-PerCP, anti-CD138-PE, and antibodies against CD11b, CD11c, and TCR conjugated to APC as a dump channel to exclude possible contaminants. DAPI was added to exclude dead cells. Live IL-10eGFP+CD138hi and IL-10eGFP-CD138hi cells were subsequently isolated on a cell sorter. The purity of the samples was always above 98%. This led to the identification of LAG-3 as a cell surface receptor specifically expressed on IL-10eGFP+CD138hi cells but not on IL-10eGFP-CD138hi cells.
LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells.
Sex, Specimen part
View SamplesIntroduction: In the recently completed Dutch GLUCOLD study, treatment of COPD patients with fluticasone salmeterol reduced the rate of decline in FEV1. These results indicate that ICS can have therapeutic efficacy in COPD. Aim: To explore the molecular mechanisms by which ICS exert their effects, we performed genome-wide gene expression profiling on bronchial biopsies from COPD patients who participated in the GLUCOLD study. Methods: An Affymetrix Human Gene Array ST version 1.0 was performed in a total of 221 bronchial biopsies that were available from 90 COPD patients at baseline and after 6 and 30 months of therapy. Linear mixed effects modeling was used to analyze treatment-specific changes in gene expression. A validation set was included and pathway analysis was performed with Gene Set Enrichment Analysis (GSEA). Results: The expression of 138 genes significantly decreased after both 6 and 30 months of treatment with fluticasone salmeterol versus placebo, whereas the expression of 140 genes increased. A more pronounced treatment-induced change in expression of 51 of these 278 genes was associated with a slower rate of decline in FEV1. Genes that decreased with treatment were involved in pathways related to cell cycle, oxidative phosphorylation, epithelial cell signaling, p53 signaling and T cell signaling. Genes that increased with treatment were involved in pathways related to focal adhesion, gap junction and extracellular matrix deposition. Conclusion: The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity. This study opens the gate to targeted and phenotype-driven therapy of COPD.
Airway gene expression in COPD is dynamic with inhaled corticosteroid treatment and reflects biological pathways associated with disease activity.
Age
View SamplesAsthma exacerbations are associated with subsequent deficits in lung function.
Decreased activation of inflammatory networks during acute asthma exacerbations is associated with chronic airflow obstruction.
No sample metadata fields
View SamplesBiological systems display extraordinary robustness. Robustness of transcriptional enhancers results mainly from clusters of binding sites for the same transcription factor, and it is not clear how robust enhancers can evolve loss of expression through point mutations. Here, we report the high-resolution functional dissection of a robust enhancer of the shavenbaby gene that has contributed to morphological evolution. We found that robustness is encoded by many binding sites for the transcriptional activator Arrowhead and that, during evolution, some of these activator sites were lost, weakening enhancer activity. Complete silencing of enhancer function, however, required evolution of a binding site for the spatially restricted potent repressor Abrupt. These findings illustrate that recruitment of repressor binding sites can overcome enhancer robustness and may minimize pleiotropic consequences of enhancer evolution. Recruitment of repression may be a general mode of evolution to break robust regulatory linkages. Overall design: 8 samples are analyzed: background GFP- and target GFP+ cells from four independent sortings.
Evolved Repression Overcomes Enhancer Robustness.
Specimen part, Subject
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