A total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR < 0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR < 0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated.
A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Disease, Disease stage
View SamplesGRBATKO_BAT_COLDEXPOSURE
The glucocorticoid receptor in brown adipocytes is dispensable for control of energy homeostasis.
Specimen part
View SamplesBALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), and the absence of TSG-6 further increases susceptibility and local inflammatory reactions, including neutrophil invasion into the joints. To gain insight into the mechanisms of TSG-6 action, synovial fibroblasts were isolated from wild-type and TSG-6-KO mice, cultured and exposed to various agents affecting either the TSG-6 expression and/or modify the intracellular function of TSG-6.
TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
Sex, Treatment
View SamplesBALB/c mice are susceptible to proteoglycan (PG) aggrecan-induced arthritis (PGIA), a murine model of rheumatoid arthritis (Glant,T.T. and Mikecz,K., Proteoglycan aggrecan-induced arthritis. A murine autoimmune model of rheumatoid arthritis. Methods Mol.Med. 2004. 102: 313-338.). However, there are marked differences among BALB/c colonies (maintained by different vendors at different locations) in PGIA onset and severity, which could be the result of subtle variations in their genetic background.
BALB/c mice genetically susceptible to proteoglycan-induced arthritis and spondylitis show colony-dependent differences in disease penetrance.
Sex
View SamplesThe selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits, which arbitrates the evolution of host defenses. Their impact, however, has seldom been documented. Here, we show with a simple mathematical model that the selective advantage of the defense system is expected to decrease with decreasing life span. We further document that, in natural populations of the model plant system Arabidopsis thaliana, the expression level of defense genes correlate positively with flowering time, a proxy for the length of vegetative life span. Using a genetic strategy to partition life span-dependent and –independent defense genes, we demonstrate that this positive co-variation is not explained by the pleiotropic action of major regulatory genes controlling both defense and life span. In agreement with our model, this study reveals that natural selection has likely assembled alleles promoting lower expression of defense genes with alleles decreasing the duration of vegetative life span in natural populations of A. thaliana. This is the first study demonstrating that life history evolution has a pervasive impact on the evolution of host immunity. Overall design: Seeds of Bur-0, Col-0 and 278 Bur-0xCol-0 Recombinant Inbred Lines (RIL) obtained after 8 generations of selfing were provided by the Arabidopsis Stock Center at INRA Versailles (France). We selected the 40 RIL in the 15% and 85% quantiles of flowering time for RNA sequencing. Each RIL and the two parental lines were planted in 20 replicates in the conditions described above. At days 14 and 28, the oldest leaf was flash-frozen in liquid nitrogen. Three pools, each combining 13 RIL, were produced at each time point for early and late lines, for a total of 3 biological replicates, 2 pool types (early and late RIL) and 2 time points (14 and 28 days). For each of the two parental lines, leaves of 12 replicates were pooled for each time point.
Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
Specimen part, Subject, Time
View SamplesmDC and pDC exhibit distinct TLR expression pattern and differ in their responses to various TLR ligands. The goal of this study was to identify genes, that were differentally expressed between mDC and pDC as a means to determine how TLR signaling pathways operate. Suprisingly, expression of TLR-assoociated signaling proteins were found to be present at equivalent levels between mDC and pDC, despite differential expression of TLRs, and thus revealing insight into use of adaptor proteins that function as general regulators of TLR signaling pathways in both cell types.
A promiscuous lipid-binding protein diversifies the subcellular sites of toll-like receptor signal transduction.
Specimen part
View SamplesThe sexually dimorphic expression of genes across 26 somatic rat tissues was using Affymetrix RAE-230 genechips. We considered probesets to be sexually dimorphically expressed (SDE) if they were measurably expressed above background in at least one sex, there was at least a two-fold difference in expression (dimorphism) between the sexes, and the differences were statistically significant after correcting for false discovery. 14.5% of expressed probesets were SDE in at least one tissue, with higher expression nearly twice as prevalent in males compared to females. Most were SDE in a single tissue. Surprisingly, nearly half of the probesets that were (SDE) in multiple tissues were oppositely sex biased in different tissues, and most SDE probesets were also expressed without sex bias in other tissues. Two genes were widely SDE: Xist (female-only) and Eif2s3y (male-only). The frequency of SDE probesets varied widely between tissues, and was highest in the duodenum (6.2%), whilst less than 0.05% in over half of the surveyed tissues. The occurrence of SDE probesets was not strongly correlated between tissues. Within individual tissues, however, relational networks of SDE genes were identified. In the liver, networks relating to differential metabolism between the sexes were seen. The estrogen receptor was implicated in differential gene expression in the duodenum. To conclude, sexually dimorphic gene expression is common, but highly tissue-dependent. Sexually dimorphic gene expression may provide insights into mechanisms underlying phenotypic sex differences.
The incidence of sexually dimorphic gene expression varies greatly between tissues in the rat.
Sex, Specimen part
View SamplesOutbred D.melanogaster populations subjected to >300 generations of natural selection on either control, or 12% ethanol, or variable food (2 replicates each) and exposed, as first instar larvae, to either water control or 12% ethanol.
Evolution of gene expression and expression plasticity in long-term experimental populations of Drosophila melanogaster maintained under constant and variable ethanol stress.
No sample metadata fields
View SamplesRoom temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable.
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease.
Specimen part, Subject
View SamplesThere is growing evidence from epidemiological and experimental studies suggesting that early life exposure to environmental chemicals can have long-term consequences that are seen in adults and not apparent early in life. We recently demonstrated that developmental exposure of zebrafish embryos to low, non-embryotoxic levels of PCB126 did not affect larval behavior but caused changes in adult behavior (Glazer et al., 2016, NeuroToxicology 52:134-143). Zebrafish embryos were exposed to either vehicle (DMSO) or low concentrations of PCB126 (0.3, 0.6, 1.2 nM) for 20 h (4–24 h post fertilization), and then reared to adulthood in clean water. Locomotor activity of the larvae at 7 and 14 days post fertilization (dpf) was not affected by PCB126. In contrast, adult fish (4 months old) tested in novel tank and shoaling assays showed impaired habituation to a novel environment. In order to investigate the underlying molecular basis of these phenotypes, we determined the transcriptional profiles in whole embryos (48 hpf), larvae (5 dpf) and adult brain (4 mo) using strand-specific RNA-sequencing. Our results show that 0.3 nM PCB126 exposure induced cyp1a transcript levels 12.5-fold in 48-hpf embryos but there was no induction in 5-dpf larvae, suggesting transient activation of aryl hydrocarbon receptor during early development. No significant induction of cyp1a was observed in the brains of adults exposed as embryos to PCB126. However, we observed significant changes in gene expression profiles in the adult brain samples. A total of 2209 and 1628 genes were differentially expressed in 0.3 nM and 1.2 nM PCB126-exposed groups, respectively. KEGG pathway analysis of differentially expressed genes in the brain suggest enrichment of genes involved in oxidative phosphorylation, neurodegenerative diseases, circadian rhythm and calcium signaling pathways. We are currently investigating the role of these genes in altered behavior observed in the adults. Overall, our results suggest that PCB exposure during sensitive periods of early development alters normal development of the brain by reprogramming gene expression patterns. [Funded by NIH P01ES021923 and NSF OCE-1314642]. Overall design: A total of 24 samples were sequenced. It includes 3 different time points and 2 or 3 different treatments. Each treatment had 3 biological replicates.
Early Life Exposure to Low Levels of AHR Agonist PCB126 (3,3',4,4',5-Pentachlorobiphenyl) Reprograms Gene Expression in Adult Brain.
No sample metadata fields
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