To unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. This particular series represents all data from d 10. The additional expression data from the time course (d8-d20) is represented by series GSE2259 ("Testicular gene expression in SCARKO mice during prepuberty").
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
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View SamplesTo unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis.
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
No sample metadata fields
View SamplesThe intestinal immune system must elicit robust immunity against harmful pathogens but restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c macrophages in the lamina propria (LP) that express several anti-inflammatory molecules including interleukin 10 (IL-10), but little or no pro-inflammatory cytokines, even upon stimulation with Toll-like receptor (TLR) ligands. These macrophages induced, in a manner dependent on IL-10, retinoic acid and exogenous transforming growth factor-, differentiation of FoxP3+ regulatory T cells. In contrast, LP CD11b+ dendritic cells elicited IL-17 production. This IL-17 production was suppressed by LP macrophages, indicating that a dynamic interplay between these subsets may influence the balance between immune activation and tolerance.
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
No sample metadata fields
View SamplesActivation of inflammatory pathways in human IBD
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Sex, Age, Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Parallel comparison of Illumina RNA-Seq and Affymetrix microarray platforms on transcriptomic profiles generated from 5-aza-deoxy-cytidine treated HT-29 colon cancer cells and simulated datasets.
Specimen part, Cell line, Treatment
View SamplesPathological bone changes differ considerably between inflammatory arthritic diseases, and most studies have focused on bone erosion. Collagen Induced Arthritis (CIA) is a model for Rheumatoid Arthritis, which, in addition to bone erosion, demonstrates bone formation at the time for clinical manifestations. The objective of this study was to use the CIA model to study bone remodelling by performing a gene expression profiling time-course study on the CIA model.
Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.
Specimen part
View SamplesThe RNA samples from HT-29 (ATCC) colon cancer cell line were reverse transcribed into cDNAs and categorized in 3 groups with different concentrations of 5-aza-deoxy-cytidine (5-Aza); in each group three replicative 150 mm cultures were treated with: 1) dimethyl sulfoxide (vehicle alone, 0 M 5-Aza); 2) 5M 5-Aza and 3) 10 M 5-Aza; for five days
Parallel comparison of Illumina RNA-Seq and Affymetrix microarray platforms on transcriptomic profiles generated from 5-aza-deoxy-cytidine treated HT-29 colon cancer cells and simulated datasets.
Specimen part, Cell line, Treatment
View SamplesSynthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TR subtype versus TR, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TR, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TR to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare.
Identical gene regulation patterns of T3 and selective thyroid hormone receptor modulator GC-1.
Specimen part, Cell line
View SamplesSalicylic acid (SA) is a critical molecule mediating plant innate immunity with an important role limiting the growth and reproduction of the virulent powdery mildew (PM) Golovinomyces orontii on Arabidopsis thaliana. To investigate this later phase of the PM interaction, and the role played by SA, we performed replicated global expression profiling for wild type and SA biosynthetic mutant ics1 Arabidopsis from 0 to 7 days post infection. We found that ICS1-impacted genes comprise 3.8% of profiled genes with known molecular markers of Arabidopsis defense ranked very highly by the multivariate empirical Bayes statistic (T2 statistic ((Tai and Speed, 2006)). Functional analyses of T2-selected genes identified statistically significant PM-impacted processes including photosynthesis, cell wall modification, and alkaloid metabolism that are ICS1-independent. ICS1-impacted processes include redox, vacuolar transport/secretion, and signaling. Our data also supports a role for ICS1 (SA) in iron and calcium homeostasis and identifies components of SA crosstalk with other phytohormones. Through our analysis, 39 novel PMimpacted transcriptional regulators were identified. Insertion mutants in one of these regulators, PUX2, results in significantly reduced reproduction of the powdery mildew in a cell death independent manner. Though little is known about PUX2, PUX1 acts as a negative regulator of Arabidopsis CDC48 (Rancour et al., 2004; Park et al., 2007), an essential AAA-ATPase chaperone that mediates diverse cellular activities including homotypic fusion of ER and Golgi membranes, ER-associated protein degradation, cell cycle progression, and apoptosis. Future work will elucidate the functional role of the novel regulator PUX2 in PM resistance.
Temporal global expression data reveal known and novel salicylate-impacted processes and regulators mediating powdery mildew growth and reproduction on Arabidopsis.
Age, Specimen part
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