Objective. To identify gene expression differences in peripheral blood from patients with early and late onset juvenile idiopathic arthritis (JIA).
Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis.
Sex, Specimen part, Race
View SamplesBiotinylated cRNA was synthesized from total RNA (Enzo; Farmingdale, NY) and processed according to the Affymetrix GeneChip Expression Analysis Technical Manual (Affymetrix; Santa Clara, CA). 57 samples: 5 pauciarticular PBMC, 15 polyarticular PBMC, 11 control PMBC, 6 JSpA PBMC, 5 pauciarticular SFMC, 10 polyarticular PBMC, 5 JSpA SFMC classified by course.
Gene expression in juvenile arthritis and spondyloarthropathy: pro-angiogenic ELR+ chemokine genes relate to course of arthritis.
No sample metadata fields
View SamplesSystemic Juvenile Idiopathic Arthritis (sJIA) has been strongly associated with macrophage activation syndrome (MAS). To better understand the pathogenesid of sJIA and to facilitate the search for MAS biomarkers, we examine gene expression profiles in untreated new onset sJIA.
Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome.
No sample metadata fields
View SamplesThe mechanisms that determine the efficacy or inefficacy of methotrexate in juvenile idiopathic arthritis (JIA) are ill-defined. The objective of this study was to identify a gene expression transcriptional signature associated with poor response to MTX in patients with JIA. RNA sequencing was used to measure gene expression in peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls. Biological differences between all JIA patients and controls were explored by constructing a signature of differentially expressed genes. Unsupervised clustering and pathway analysis was performed. Transcriptional profiles were compared to a reference gene expression database representing sorted cell populations, including B and T lymphocytes, and monocytes. A signature of 99 differentially expressed genes (Bonferroni-corrected p<0.05) capturing the biological differences between all JIA patients and controls was identified. Unsupervised clustering of samples based on this list of 99 genes produced subgroups enriched for MTX response status. Comparing this gene signature to reference signatures from sorted cell populations revealed high concordance between the expression profiles of monocytes and of MTX non-responders. CXCL8 (IL-8) was the most significantly differentially expressed gene transcript comparing all JIA patients to controls (Bonferroni-corrected p=4.12E-10). Variability in clinical response to methotrexate in JIA patients is associated with differences in gene transcripts modulated in monocytes. These gene expression profiles may provide a basis for biomarkers predictive of treatment response. Overall design: Peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls
Transcriptional profiles of JIA patient blood with subsequent poor response to methotrexate.
Subject
View SamplesObjective: A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. Methods: PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. Results: 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of gene associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these components differentially-expressed in the other three subtypes. Conclusions: Expression analysis identified differentially expressed genes in PBMCs between subclasses of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis.
Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis.
Sex, Specimen part, Race
View SamplesChronic kidney disease (CKD) is the gradual, asymptomatic loss of kidney function and current tests only identify it when significant loss has already happened. Using RNA sequencing in a mouse model of folic acid (FA) induced nephropathy, here we report the identification of 10 genes that track kidney fibrosis development, the common pathological finding in CKD patients. The gene expression of all 10 candidates was confirmed to be significantly high (~ 10-150 fold) in three well-established and mechanistically distinct mouse models of kidney fibrosis. Protein expression was also high in the FA model as well as patients with biopsy-proven kidney fibrosis. The specificity of these 10 candidates for kidney fibrosis was demonstrated by showing a very modest (~ 2-5 fold) increase in the mouse models of acute kidney injury as well as following liver fibrosis in mice and humans. Using targeted selected reaction monitoring mass spectrometry (SRM-MS) we found that 3 out of 10, cadherin 11 (CDH11), mannose receptor C1 (MRC1), phospholipid transfer protein (PLTP), are detectable in human urine. Furthermore, the levels of CDH11 and MRC1 are able to distinguish patients with chronic kidney disease from healthy individuals (n = 78, p<0.01). In summary, we report the identification of CDH11 and MRC1 as novel non-invasive biomarkers of CKD. Overall design: mRNA sequencing of mouse kidney before and at various time points (1,2,3,7 & 14 days) after intraperitoneal treatment with folic acid.
RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis.
No sample metadata fields
View SamplesInosine 5''-phosphate dehydrogenase (impdh) has been well known as a key enzyme in GTP biosynthesis pathway. We found that three isoforms of impdh in zebrafish, namely impdh1a, impdh1b and impdh2, all show robust circadian expression.To examine the molecular functions of three impdh isoforms in zebrafish on the genome scale, we measured the global expression changes of impdh1a, impdh1b and impdh2 morpholino injected larvae (morphants) respectively using RNA-seq. Wild type (WT), control and three impdh morphants were collected at 32 hpf. In our RNA-seq result, we identified 468, 331 and 1166 significant genes affected by impdh1a, impdh1b and impdh2 morpholino (MO) knock-down respectively. Among them, there are limited overlaps between genes affected by different MOs and only 36 genes in common among all three MOs. This indicates that the three impdh isoforms have distinct molecular functions. Overall design: To knock down the target genes, three impdh MOs and control MO were pressure-injected into 1- to 2-cell stage embryos. WT, control and three impdh morphants were raised at 28°C under 14h: 10h light/dark cycle from birth and sampled simultaneously at 32 hpf. Each group has at least 40 embryos.
Integrative analysis of circadian transcriptome and metabolic network reveals the role of de novo purine synthesis in circadian control of cell cycle.
No sample metadata fields
View SamplesObjective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis.
Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity.
Specimen part
View SamplesAltered daily patterns of hormone action are suspected to contribute to metabolic disease. It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism. Here, we examined diurnal metabolite and transcriptome patterns in a zebrafish glucocorticoid deficiency model by RNA-Seq, NMR spectroscopy and liquid chromatography-based methods. We observed dysregulation of metabolic pathways including glutaminolysis, the citrate and urea cycles and glyoxylate detoxification. Constant, non-rhythmic glucocorticoid treatment rescued many of these changes, with some notable exceptions among the amino acid related pathways. Surprisingly, the non-rhythmic glucocorticoid treatment rescued almost half of the entire dysregulated diurnal transcriptome patterns. A combination of E-box and glucocorticoid response elements is enriched in the rescued genes. This simple enhancer element combination is sufficient to drive rhythmic circadian reporter gene expression under non-rhythmic glucocorticoid exposure, revealing a permissive function for the hormones in glucocorticoid-dependent circadian transcription. Our work highlights metabolic pathways potentially contributing to morbidity in patients with glucocorticoid deficiency, even under glucocorticoid replacement therapy. Moreover, we provide mechanistic insight into the interaction between the circadian clock and glucocorticoids in the transcriptional regulation of metabolism. Overall design: RNA-Seq from total RNA of zebrafish larvae during (5 dpf) the diurnal cycle. Time-series mRNA profiles of untreated wild type (WT), rx3t25327/t25327 [rx3 strong] and rx3t25181/t25181 [rx3 weak] mutant larvae as well as dexamethasone treated WT and rx strong larvae were generated by deep sequencing.
Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids.
No sample metadata fields
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