Posttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.
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View SamplesThe SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Age
View SamplesAims: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5’ splice site to an upstream 3’ splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts.[1,2] Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments.Methods and Results: Deep RNA sequencing of cardiomyocyte development and ß-adrenergic stimulation uncovered 4,518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intri-guingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes.Conclusion: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene inde-pendent expression dynamics in patient samples and may interact with the ribo-some and RISC complex. In summary, the hiPSC-CM model uncovered a new sig-nature of potentially disease relevant circRNAs which may serve as novel therapeu-tic targets.
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Sex, Specimen part, Race
View SamplesThe three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Significant and systematic expression differentiation in long-lived yeast strains.
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View SamplesRecent studies suggest vitamin D deficiency is associated with chronic lung diseases such as asthma and chronic obstructive pulmonary disease. Each of these are characterised by airway hyperresponsiveness (AHR) and airway remodeling, the latter characterized by increased airway smooth muscle (ASM) mass. In this study we investigated the biological mechanisms underlying increased ASM mass and AHR due to vitamin D deficiency via RNA-seq transcriptome analysis of female BALB/c mice at 8 weeks of age.
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View SamplesRNA expression in adipose and skin from women with polycystic ovary syndrome (PCOS) was examined using RNA sequencing (Illumina HiSeq 50 cycle single-read sequencing) as a function of the genotype at 16 PCOS genetic risk variants. We hypothesized that the tissue expression pattern in adipose and skin would help identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci.
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Sex, Age, Specimen part
View SamplesHigh-throughput sequencing of RNA (RNA-Seq) in human cancer shows remarkable potential to simultaneously identify expression levels of protein-coding genes and long non-coding RNAs (lncRNAs). We performed RNA-Seq to investigate expression level of lncRNAs and protein-coding genes in 30 esophageal samples, including 15 esophageal squamous cell carcinoma (ESCC) tissue samples and 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE (for unsupervised random walk with each dysregulated lncRNA/PCG), to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. By this method, multiple known cancer and novel potentially functional lncRNAs were effectively identified. Quantitative reverse-transcription PCR was performed to confirm the lncRNA expression level of eight novel functional lncRNAs in an additional 120 paired ESCC patient samples. Finally, we characterized lncRNA625 as a novel ESCC regulator of cell proliferation, invasion and migration. Moreover, we identified E1A-binding protein p300 (EP300) as playing a key role in executing lncRNA625-induced transcriptional responses. These findings establish the utility of integrative bioinformatics analyses of RNA-Seq to identify cancer-associated functional lncRNAs.
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View SamplesWe report a comprehensive large-scale expression profiling analysis of mammalian male germ cells undergoing mitotic growth, meiosis and gametogenesis using High Density Oligonucleotide Microarrays and highly enriched cell populations. Among 11955 rat loci investigated, 1268 were identified as differentially transcribed in germ cells at subsequent developmental stages as compared to total testis, somatic Sertoli cells as well as brain and skeletal muscle controls. The loci were organized into four expression clusters that correspond to somatic, mitotic, meiotic and post-meiotic cell types. This work provides information about expression patterns of approximately 200 genes known to be important during male germ cell development. Approximately 40 of those are included in a group of 121 transcripts for which we report germ cell expression and lack of transcription in three somatic control cell types. Moreover, we demonstrate the testicular expression and transcriptional induction in mitotic, meiotic and/or post-meiotic germ cells of 293 as yet uncharacterized transcripts some of which are likely to encode factors involved in spermatogenesis and fertility. This group also contains numerous potential germ cell specific targets for innovative contraceptives. A graphical display of the data is conveniently accessible through the GermOnline database at <a href="http://www.germonline.org" target="_blank">http://www.germonline.org</a>.
Expression profiling of mammalian male meiosis and gametogenesis identifies novel candidate genes for roles in the regulation of fertility.
Sex, Age, Specimen part
View SamplesCH causes perivascular inflammation, enhanced pulmonary arterial constriction and remodeling leading to the development of pulmonary hypertension. Pulmonary hypertension is a debilitating disease with a high mortality rate. CH develops in patients with chronic obstructive pulmonary disease (COPD), sleep apnea or people living at high altitude. Both COPD and sleep apnea are very prevalent and pulmonary hypertension develops in a large % of COPD and sleep apnea patients. The molecular mechanisms that underlie the development of CH-induced pulmonary hypertension are far from clear. We have previously demonstrated that CH activates the Ca2+/calcineurin-regulated transcription factor NFATc3 in PASMC and that NFATc3 is required for CH-induced pulmonary hypertension in mice. Although this work was the first to identify a role for this transcription factor in an experimental model of pulmonary hypertension, since a conventional whole animal KO was used it is unknown if PASMC NFATc3 contributes to CH-induced PH. Furthermore, the genes regulated by NFATc3 in PASMC under control and CH conditions are largely unknown.
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Sex, Age, Specimen part, Treatment
View SamplesThe transcriptome of the three atino80 allelic mutants was compared to that of wild-type and 50B Arabidopsis plants (see Fritsch et al. 2004). Since the transcriptomes of 50B and wild-type plants were found to be identical, we compared expression in the mutant with 50B and with wild-type without distinction. Therefore, we had four replicates of the wild type condition (50B line, wild-type) and two replicates for each of the mutant alleles (atino80-1, atino80-2 and atino80-3), all ecotype Columbia. All lines were profiled in duplicate (grown independently at 2-week-intervals).
The INO80 protein controls homologous recombination in Arabidopsis thaliana.
Age, Specimen part
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