Filters
Technology
Platform
GSE89253
Homo sapiens
125 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epipolymorphisms associated with the clinical outcome of autoimmune arthritis affect CD4+ T cell activation pathways.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 125 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Multifactorial diseases, including autoimmune juvenile idiopathic arthritis (JIA), result from a complex interplay between genetics and environment. Epigenetic mechanisms are believed to integrate such gene-environment interactions, fine-tuning gene expression and possibly contributing to immune system dysregulation. Although anti-TNF therapy has strongly increased JIA remission rates, it is not curative and up to 80% of patients flare upon treatment withdrawal. Thus, a crucial unmet medical and scientific need is to understand the immunological mechanisms associated with remission or flare to inform clinical decisions. Here, we explored the CD4+ T cell DNA methylome of 68 poly-articular and extended oligo-articular JIA patients, before and after anti-TNF therapy withdrawal, to identify features associated with maintenance of inactive disease (ID). Individual CpG sites were clustered in coherent modules without a priori knowledge of their function through network analysis. The methylation level of several CpG modules, specifically those enriched in CpG sites belonging to genes that mediate T cell activation, uniquely correlated with clinical activity. Differences in DNA methylation were already detectable at the time of therapy discontinuation, suggesting epigenetic predisposition. RNA profiling also detected differences in T cell activation markers, including HLA-DR, but, overall, its sensitivity was lower than epigenetic profiling. Changes to the T cell activation signature at the protein level were detectable by flow cytometry, confirming the biological relevance of the observed alterations in methylation. Our work proposes, for the first time, epigenetic discrimination between clinical activity states, and reveals T cell-related biological functions tied to, and possibly predicting and/or causing, clinical outcome.
Publication Title
Epipolymorphisms associated with the clinical outcome of autoimmune arthritis affect CD4+ T cell activation pathways.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 68 Downloadable Samples
Illumina HiSeq 2000
Description
Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways have been shown to contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways responsible for the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, only two PRR pathways – the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways - were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated an inflammatory program, STING signaling activated an antiviral/type I interferon response, and both pathways contributed to a program linking innate and adaptive immunity. Only a small number of genes were induced in the absence of TLR or STING signaling, and these genes possessed a strong hypoxia signature. STING pathway activation required live S. aureus and was largely dependent on the DNA sensor cyclic guanosine-adenosine synthase (cGAS) recognition of S. aureus DNA. Interestingly, using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus, with TLR signaling being required for protective interleukin (IL)-1? and neutrophil recruitment and STING signaling having an opposite effect. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered byS. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus. Overall design: Files are labeled according to the figures in which they were used. Note, that many data files were used in multiple figures or figure panels. Files are labeled by genotype of macrophages (WT=wildtype; KO= StingGt/Gt; DKO=MyD88-/-TRIF-/-) and whether the macrophages were treated with live (Live) or heat killed (HK) or uninfected (zero hour). Labeling of time points is in the order of "minutes_replicate #." For example, "WT_HK_30_2" indicates that this is wild type mouse macrophages stimulated with heat killed bacteria at the 30-minute time point and is replicate number 2. Reads were converted into RPKM, and the RPKM for all replicates listed for a given time point were averaged to obtain the average RPKM that was used for figures and analyses. For samples listed as contributing to either figure 3 or supplemental figure 2, the replicates that do NOT end in either KO_analysis nor DKO analysis were used to determine induced genes in wild type macrophages. In contrast, the replicates that end in KO_analysis or DKO_analysis were used to determine dependence on either STING signaling or MyD88/TRIF signaling, respectively. If a replicate was used in the STING or MyD88/TRIF dependence analysis for both live and heat-killed S. aureus, "live_and_hk" was added after the dependence analysis it contributed to. Some 0h samples were used in both live and heat-killed analyses.
Publication Title
Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Sensitive versus Resistant patient-derived colorectal cancer tumor xenografts with PIK3CA mutant against saracatinib (AZD0530)
Publication Title
Common PIK3CA mutants and a novel 3' UTR mutation are associated with increased sensitivity to saracatinib.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 107 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Gene expression was analysed in the colon and brain of normal rat pups from late prenatal through early postnatal development. Tissue was isolated from pups one day prior to the anticipated date of birth and throughout the suckling period until the end of weaning.
Publication Title
Sialic acid utilisation and synthesis in the neonatal rat revisited.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to detect the primary changes caused by the 'san' mutation in Roquin gene by comparing the gene expression profiles of naive (CD44lo) CD8+ T cell population.
Publication Title
Breakdown in repression of IFN-γ mRNA leads to accumulation of self-reactive effector CD8+ T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- NextSeq 500
Description
To characterize the effect of CSGG in dendritic cell phenotypic changes, we performed gene expression RNAseq analysis for Mock and CSGG treated splenic dendritic cells after 0h, 4h and 8h of CSGG treatment. Overall design: Total RNA was extracted from splenic dendritic cells of mock and CSGG treated group.
Publication Title
Cell surface polysaccharides of <i>Bifidobacterium bifidum</i> induce the generation of Foxp3<sup>+</sup> regulatory T cells.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Zea mays
- 36 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cis-transcriptional variation in maize inbred lines B73 and Mo17 leads to additive expression patterns in the F1 hybrid.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 30 Downloadable Samples
- Illumina HiSeq 2000
Description
We found that the midgut shows striking regional differentiation along its anterior-posterior axis. Ten distinct subregions differ in cell morphology, gene expression and aspects of Notch signaling. RNA from isolated regions that was analyzed by RNAseq revealed spatially regulated expression of hundreds of enzymes and other genes with likely tissue functions. Overall design: 10 midgut segments comprising from 1-3 subregions x 3 replicates from each segment = 30 samples
Publication Title
Physiological and stem cell compartmentalization within the Drosophila midgut.
Sample Metadata Fields
Cell line, Subject
View Samples- Zea mays
- 12 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Microarray analysis of gene expression patterns in immature ear, seedling, and embryo tissues from the maize inbred lines B73 and Mo17 identified numerous genes with variable expression. Some genes had detectable expression in only one of the two inbreds; most of these genes were detected in the genomic DNA of both inbreds, indicating that the expression differences are likely caused by differential regulation rather than by differences in gene content. Gene expression was also monitored in the reciprocal F1 hybrids B73xMo17 and Mo17xB73. The reciprocal F1 hybrid lines did not display parental effects on gene expression levels. Approximately 80% of the differentially expressed genes displayed additive expression patterns in the hybrids relative to the inbred parents. The approximately 20% of genes that display nonadditive expression patterns tend to be expressed at levels within the parental range, with minimal evidence for novel expression levels greater than the high parent or less than the low parent. Analysis of allele-specific expression patterns in the hybrid suggested that intraspecific variation in gene expression levels is largely attributable to cis-regulatory variation in maize. Collectively, our data suggest that allelic cis-regulatory variation between B73 and Mo17 dictates maintenance of inbred allelic expression levels in the F1 hybrid, resulting in additive expression patterns.
Publication Title
Cis-transcriptional variation in maize inbred lines B73 and Mo17 leads to additive expression patterns in the F1 hybrid.
Sample Metadata Fields
No sample metadata fields
View Samples