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GSE14365
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aire is an important transcription regulator that mediates a role in central tolerance via promoting the promiscuous expression of tissue-specific antigens in the thymus. Although several mouse models of Aire-deficiency have been described, none has analysed the phenotype induced by a mutation that emulates the common 13bp deletion in human APECED by disrupting the first PHD domain in exon 8. Aire-deficient mice with a corresponding mutation showed some disturbance of the medullary epithelial compartment, but at the phenotypic level their T cell compartment appeared relatively normal in the thymus and periphery. An increase in the number of activated T cells was evident, and autoantibodies against several organs were detected. At the histological level, lymphocytic infiltration of several organs indicated the development of autoimmunity, though symptoms were mild and quality of life for Aire-deficient mice appeared equivalent to wild-type littermates, with the exception of male infertility. Vbeta and CDR3 length analysis suggested that each Aire-deficient mouse developed it own polyclonal autoimmune repertoire. Finally, given the prevalence of candidiasis in APECED patients, we examined the control of infection with Candida albicans in Aire-deficient mice. No increase in disease susceptibility was found for either oral or systematic infection. These observations support the view that additional genetic and/or environmental factors contribute substantially to the overt nature of autoimmunity associated with Aire mutations, even for mutations identical to those found in humans with APECED.
Publication Title
Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Examined gene expression changes in a histone H2A R78A mutant in Saccharomyces cerevisiae relative to wild-type cells. THe overall goal of this study was to determine the functions of histone 'sprocket' arginine residues, which insert into the DNA minor groove in the nucleosome. We examined the roles of sprocket arginine mutants in gene expression, histone incorporation, and DNA repair.
Publication Title
Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Genetic disruption of thioredoxin reductase 1 protects against acetaminophen (APAP) toxicity.
Publication Title
A Txnrd1-dependent metabolic switch alters hepatic lipogenesis, glycogen storage, and detoxification.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 115 Downloadable Samples
Illumina HiScanSQ
Description
The 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.
Publication Title
Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established.
Publication Title
Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 29 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Wild-type laboratory strains of model organisms are typically kept in isolation for many years, with the action of genetic drift and selection on mutational variation causing lineages to diverge with time. Natural populations from which such strains are established, show that gender-specific interactions in particular drive many aspects of sequence level and transcriptional level variation. Here, our goal was to identify genes that display transcriptional variation between laboratory strains of Drosophila melanogaster, and to explore evidence of gender-biased interactions underlying that variability.
Publication Title
Variable sexually dimorphic gene expression in laboratory strains of Drosophila melanogaster.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PRDM5 is a recently identified member of the PRDM family of proteins, which functions as a transcriptional repressor by recruiting histone methyltransferase G9A to DNA, and behaves as a putative tumor suppressor in different types of cancer.
Publication Title
The tumor suppressor PRDM5 regulates Wnt signaling at early stages of zebrafish development.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 12 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Pseudomonas aeruginosa displays tremendous metabolic diversity, controlled in part by the abundance of transcription regulators in the genome. We have been investigating P. aeruginosas response to the host, particularly changes regulated by the host-derived quaternary amines choline and glycine betaine (GB). We previously identified GbdR as an AraC-family transcription factor that directly regulates choline acquisition from host phospholipids (via binding to plcH and pchP promoters), is required for catabolism of the choline metabolite GB, and is an activator that induces transcription in response to GB or dimethylglycine. Our goal was to characterize the GbdR regulon in P. aeruginosa using genetics and chemical biology in combination with transcriptomics and in vitro DNA-binding assays. Here we show that GbdR activation regulates transcription of 26 genes from 12 promoters; 11 of which have measureable binding to GbdR in vitro. The GbdR regulon includes the genes encoding GB, dimethylglycine, sarcosine, glycine, and serine catabolic enzymes, and the BetX and CbcXWV quaternary amine transport proteins. . Additionally, identification of two uncharacterized regulon members suggests roles for these proteins in response to choline metabolites.
Publication Title
Characterization of the GbdR regulon in Pseudomonas aeruginosa.
Sample Metadata Fields
Treatment
View Samples- Gallus gallus
- 28 Downloadable Samples
- Illumina Genome Analyzer II
Description
RNAseq analysis of caecal tissue from 14 C. jejuni-susceptible and 14 C. jejuni-resistant birds from a single population of infected chickens was conducted in order to identify gene expression associated with resistance to colonization. Significantly higher expression of genes involved in the innate immune response, cytokine signaling, B cell and T cell activation and immunoglobulin production, as well as the renin-angiotensin system was observed in resistant birds. Overall design: A population of 255 Barred Rock chickens were orally inoculated with C. jejuni and their caecal colonization levels estimated 48 hours post-inoculation. Caecal samples from 14 birds with no colonization and the 14 birds with the highest colonization were selected for mRNA sequencing.
Publication Title
Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Whole genome microarrays were probed with total mRNA from PTD-DRBD GAPDH siRNA treated H1299 cells at 12 h and 24 h. Using a 1.6x fold increase/decrease filter of cellular mRNAs, we detected a dramatic reduction in the target GAPDH mRNA along with a limited number of both up and down regulated genes. The up regulated genes were reduced in numbers and to nearly background 1.6x levels at 24 h, while the down regulated genes increased slightly in numbers and maintained a similar magnitude at 24 h. In contrast, lipofection treated cells showed both a dramatic increase in both the total number of genes altered and the magnitude of the increase. In addition, the numbers of genes affected increased between 12 h and 24 h, suggesting that lipofection of siRNAs into cells results in a substantial alteration to the transcriptome and may thereby confound interpretation of experimental outcomes. Moreover, the GAPDH specific knockdown was significantly smaller than PTD-DRBD mediated knockdown.
Publication Title
Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein.
Sample Metadata Fields
Cell line, Time
View Samples