Noncommunicable chronic respiratory diseases (CRDs) such as chronic obstructive pulmonary disease (COPD) and asthma affect hundreds of millions of people and are associated with increasing morbidity and mortality. CRDs are multifactorial disorders and despite different etiologies they commonly manifest in pulmonary structural (airway remodeling, emphysema) and/or functional changes. In this study we used mice intrinsically developing autoimmune-mediated lung inflammation associated with lung pathology and immune imprinting partly comparable to hallmarks of CRD. The so called SPC-HAxTCR-HA transgenic mice (BALB/c genetic background), express a neo-self antigen (influenza A virus hemagglutinin, HA) on lung alveolar epithelial type II cells in the presence of HA-specific CD4+ T cells leading to the establishment of chronic lung inflammation. In order to characterize the inflammatory lung milieu of SPC-HAxTCR-HA mice in comparison to SPC-HA control mice (lacking HA-specific CD4+ T cells), we performed whole lung tissue transcriptional analyses (n = 3 / group). 378 transcripts were found to be differentially expressed in SPC-HAxTCR-HA lungs. 326 of those were up-regulated and 52 were down-regulated compared to SPC-HA control mice.
Chronic lung inflammation primes humoral immunity and augments antipneumococcal resistance.
Sex, Age, Specimen part
View SamplesBackground:
Role of IFN-gamma and IL-6 in a protective immune response to Yersinia enterocolitica in mice.
Sex
View SamplesOrogastral infection of mice with Yersinia enterocolitical leads to HIF-1 alpha activation.To elucidate whether this HIF-1 alpha activation also results in a HIF-1 dependent gene programming, the transcriptomes from Peyers Patches of uninfected and Yersinia enterocolitica infected mice were analyzed by means of of microarray analyses using Affymetrix GeneChip probe arrays (MG-U74Av2). In total, 288 genes were differentially regulated three day after infection in PP compared with the expression of uninfected control mice. Of these 288 genes, 217 were found to be differentially upregulated and from these, 14 genes ( 6.5% of all upregulated genes) are well described to be regulated via HIF-1. These data indicate that orogatral infection with Y. enterocolitica results in HIF-1 dependent gene programmning
Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores.
No sample metadata fields
View SamplesHuman endogenous retroviruses (HERV) are relics of ancient retroviral infections in our genome. Most of them have lost their coding capacity, but proviral RNA or protein have been observed in several disease states (e.g. in inflammatory and autoimmune diseases and malignancies). However, their clinical significance as well as their mechanisms of action have still remained elusive. As human aging is associated with several biological characteristics of these diseases, we now analyzed the aging-associated expression of the individual proviruses of two HERV families, HERV-K (91 proviruses) and HERV-W (213 proviruses) using genome-wide RNA-sequencing (RNA-seq). RNA was purified from blood cells derived from healthy young individuals (n=7) and from nonagenarians (n=7). The data indicated that in the case of HERV-K (HML-2) 33 proviruses had a detectable expression but in only 3 of those the expression levels were significantly different between the young and old individuals. In the HERV-W family expression was observed in 45 loci and only in one case the young/old difference was significant. However, applying the hierarchical clustering on the HERV expression data resulted in the formation of two distinct clusters, one containing the young individuals and another the nonagenarians. This suggests, that even though the aging-associated differences in the expression levels of individual proviruses are minor, there seems to be some underlying aging-related pattern. These data indicate that aging does not have a strong effect on the expression of individual HERV proviruses, but instead several proviruses are affected moderately, leading to age-dependent expression profiles. Overall design: Seven peripheral blood mononuclear cell (PBMC) samples from healthy nonagenarians, aged 94, all female. Seven PBMC samples from healthy young laboratory personnel, aged 26 to 32 median age 28, all female. RNA-sequencing of the samples was done. Expression of genes and human endogenous retroviruses (HERVs) was quantified.
Effect of aging on the transcriptomic changes associated with the expression of the HERV-K (HML-2) provirus at 1q22.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Phytol is lethal for Amacr-deficient mice.
Sex, Specimen part
View SamplesBile acids play multiple roles in vertebrate metabolism by facilitating lipid absorption in the intestine and acting as a signaling molecule in lipid and carbohydrate metabolism. Bile acids are also the main route to excrete excess cholesterol out of the body. Alpha-methyl-Coa racemase (Amacr) is one of the enzymes needed to produce bile acids from cholesterol. The mouse model lacking Amacr can produce only minor (less than 10%) amounts of bile acids, but still they are symptomless in normal laboratory conditions.
Phytol is lethal for Amacr-deficient mice.
Sex, Specimen part
View SamplesBile acids play multiple roles in vertebrate metabolism by facilitating lipid absorption in the intestine and acting as a signaling molecule in lipid and carbohydrate metabolism. Bile acids are also the main route to excrete excess cholesterol out of the body. Alpha-methyl-Coa racemase (Amacr) is one of the enzymes needed to produce bile acids from cholesterol. The mouse model lacking Amacr can produce only minor (less than 10%) amounts of bile acids, but still they are symptomless in normal laboratory conditions.
Phytol is lethal for Amacr-deficient mice.
Sex, Specimen part
View SamplesChromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (=3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type-specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type-specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases. Overall design: Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project. NISC Comparative Sequencing Program
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.
No sample metadata fields
View SamplesOn the basis of the cell-surface molecule expression, CD16+ monocytes are likely comprised of distinct subpopulations of monocytes rather than a continuum of CD14+ monocytes with differing levels of cell activation. To better study this, we used gene array analysis that compared overall gene expression profiles of CD16+ subpopulations (CD14+CD16+ and CD16+) with that of CD14+CD16-. Gene expression in three FACS-sorted monocyte subsets was assessed by Affymetrix rhesus macaque oligonucleotide gene arrays that contain 52,024 probe sets covering 47,000 monkey genes. There were 29,361 probe sets that expressed in at least one subpopulation (raw array signal intensity > 32). Raw data were processed using robust multi-array average. To identify the most strongly, differentially expressed genes in each subpopulation, we only selected transcripts with consistently greater than four-fold difference (P < .05). In comparison to CD14+CD16- monocyte subset, a large number of genes (9098/29361, 30.9%) were differentially expressed in both CD14+CD16+ and CD16+ subsets: 1999 genes down-regulated; and 7099 genes up-regulated. Altogether, we observed large-scale gene expression differences between the CD14+CD16- subset and the two CD16+ subsets (CD14+CD16+ and CD16+), demonstrating transcriptional heterogeneity. The differential gene expression between CD16- and CD16+ monocytes underscore the fundamental differences between these cells.
Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of immune-competent human cells exposed to engineered zinc oxide or titanium dioxide nanoparticles.
Specimen part, Treatment, Time
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