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GSE71370
Homo sapiens
26 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CD14+ monocytes sorted from the synovial fluid or peripheral blood of rheumatoid arthritis patients were analyzed by full transcriptome microarray analysis. Monocytes from healthy control samples (peripheral blood) were also profiled.
Publication Title
MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
To follow-up findings that miR-9 was abundantly expressed in control NPCs, significantly down-regulated in a subset of SZ NPCs, and that miR-9 levels/activity, neural migration and diagnosis were strongly correlated, we tested the effect of manipulating miR-9 at cellular, proteomic and transcriptomic levels. Unexpectedly, proteomic- and RNAseq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients. Methods: We compared global transcription of forebrain NPCs from two control and two SZ patients with manipulated miR-9 levels by RNAseq. Results: Although RNAseq analysis revealed large inter-individual heterogeneity, we were able to resolve several functional consistencies in the effects of our miR-9 perturbations: i) the change in miR-9 activity was consistent with the inhibitory role of miR-9, ii) the gene expression fold-change of miR-9 target genes (between each perturbation and its corresponding control, summarized by the first principal component) was correlated (r=0.95, p=3.92e-04) with miR-9 fold change and iii) the differentially expressed (DE; p <0.01) gene list resulting from miR-9 perturbation (paired t-test) was enriched for miR-9 targets (1.53-fold, p=1.2e-5). Conclusions: We integrated the miR-9 perturbation RNAseq data with our existing RNAseq datasets contrasting control and SZ hiPSC NPC expression from our cohort 1 (six controls, four patients), to ask whether there was any relationship between the “SZ NPC signature” and “miR-9 perturbation” datasets; we observed that the DE (p-value <0.01) in “SZ NPC signature” is enriched for DE (fdr<0.01) in “miR-9 perturbation” (the overall enrichment is 2.31-fold (p=9.39e-09)); there is significant correlation between DE fold-change in these two datasets (overall genes r=0.188; p<10e-50). Effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes Overall design: Biological duplicates of passage-matched NPCs from 1 control (female) and 1 SZ patient (female) were transduced with either RV-GFP or RV-miR-9-GFP; GFP-positive NPCs were purified by fluorescent activated cell sorting (FACS) and expanded for two passages. In parallel, passage-matched NPCs from 2 controls (1 male, 1 female) and 2 SZ patients (1 male, 1 female) were transiently transfected with either scrambled or miR-9 LNA probes. In both instances, miR-9 perturbation was confirmed by qPCR.
Publication Title
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). Overall design: 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.
Publication Title
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Escherichia coli 8624 and the isogenic mutants in qseE, qseF and qseG are compared to determine the role that each of the genes play in regulation of the transcriptome. These results are verified by qRT-PCR and reveal the important role of this three-component signaling system.
Publication Title
The two-component system QseEF and the membrane protein QseG link adrenergic and stress sensing to bacterial pathogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Pre-stimulation of MDMs with LPS (signals via MyD88 and TRIF dependent pathways) and PolyI:C (signals via a TRIF dependent pathway) leads to a reduced viral infection. In contrast, pre-stimulation with P3C (signals via MyD88 dependent pathway) does not lead to a reduced viral infection. This microarray was performed to find genes that are specifically upregulated in LPS and PolyI:C stimulated MDMs but not P3C stimulated MDMs. So to give us leads into the mechanism involved in the reduction of viral infection.
Publication Title
Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Reports that low-intensity microwave radiation can induce heat-shock reporter gene expression in the nematode, Caenorhabditis elegans, have recently been reinterpreted as a subtle thermal effect caused by very slight heating. This study used a microwave exposure system (1.0 GHz, 0.5 W power input; SAR 0.9-3 mW kg-1 for 6-well plates) that minimises the temperature differential between sham and exposed conditions to 0.1C. Comparable measurement and simulation studies of SAR distribution within this exposure system are presented. We compared 5 Affymetrix gene-arrays of pooled triplicate RNA populations from sham-exposed L4/adult worms against 5 gene-arrays of pooled RNA from microwave-exposed worms (taken from the same source population in each run). Few genes showed consistent expression changes across all 5 comparisons, and all such expression changes appeared modest after applying standard normalisation procedures ( 30% up- or down-regulated). The number of statistically significant differences in gene expression (846) was less than the false-positive rate expected by chance (1131). As one example, an apparent up-regulation of the vit-3 vitellogenin gene by microwave exposure was not mirrored by similar changes affecting the other co-regulated members of the same vit gene family. We conclude that the pattern of gene expression in L4/adult C elegans is not substantially perturbed by low-intensity microwave radiation, and that the minor changes observed in this study may well be explicable as false positives. As a check on the sensitivity of the Affymetrix gene-arrays used, we also compared RNA samples from N2 worms subjected to a sub-heat-shock treatment (28C) against controls kept at 26 C (but using only 2 gene arrays per condition). After similar normalisation, many more genes (3712) showed substantial expression changes (i.e. > 2-fold at p < 0.05), including a group of six heat-shock genes which were strongly but unexpectedly down-regulated (by > 10-fold). However, further replication and confirmation by real-time RT-PCR would be needed to establish how many of these changes might also be false positives.
Publication Title
Low-intensity microwave irradiation does not substantially alter gene expression in late larval and adult Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 190 Downloadable Samples
- Illumina HiSeq 2500
Description
Airway epithelial cells and macrophages differ markedly in their responses to influenza A virus (IAV) infection. To investigate transcriptional responses underlying these differences, purified subsets of type II airway epithelial cells (ATII) and alveolar macrophages (AM) recovered from the lungs of mock- or IAV-infected mice were subjected to RNA sequencing. In the absence of infection, AM predominantly expressed genes related to immunity whereas ATII expressed genes consistent with their physiological roles in the lung. Following IAV infection, AM almost exclusively activated cell-intrinsic antiviral pathways that were dependent on interferon regulatory factor (IRF)3/7 and/or type I interferon (IFN) signaling. In contrast, IAV-infected ATII activated a broader range of physiological responses, including cell-intrinsic antiviral pathways, which were both independent and dependent on IRF3/7 and/or type I IFN. These data suggest that transcriptional profiles hardwired during development could be a major determinant underlying the different responses of ATII and AM to IAV infection. Overall design: 96 samples were analyzed: (A) 4 replicates of HA+ Alveolar Macrophage (AM) and 4 replicates of CD103+ Dendritic cells (DC) isolated from the lung lobes of C57/BL6 mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) AM and 4 replicates of mock-infected (HA-) CD103+ DC isolated from the lung lobes of mock-infected C57/BL6 mice on 9 h p.i. with allantoic fluid of equal dilution as PR8. 4 replicates of HA+ Airway epithelial cell Type II (ATII) and 4 replicates of HA+ Ciliated Cell (CC) isolated from the lung lobes of C57/BL6 mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) ATII and 4 replicates of mock-infected (HA-) CC isolated from the lung lobes of mock-infected C57/BL6 mice on 9 h p.i. with allantoic fluid of equal dilution as PR8. (B) 4 replicates of HA+ AM and 4 replicates of CD103+ DC isolated from the lung lobes of IFNAR2-/- mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) AM and 4 replicates of mock-infected (HA-) CD103+ DC isolated from the lung lobes of mock-infected IFNAR2-/- mice on 9 h p.i. with allantoic fluid of equal dilution as PR8. 4 replicates of HA+ ATII and 4 replicates of HA+ CC isolated from the lung lobes of IFNAR2-/- mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) ATII and 4 replicates of mock-infected (HA-) CC isolated from the lung lobes of mock-infected IFNAR2-/- mice on 9 h p.i. with allantoic fluid of equal dilution as PR8. (C) 4 replicates of HA+ AM and 4 replicates of CD103+ DC isolated from the lung lobes of IRF3/7-/- mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) AM and 4 replicates of mock-infected (HA-) CD103+ DC isolated from the lung lobes of mock-infected IRF3/7-/- mice on 9 h p.i. with allantoic fluid of equal dilution as PR8. 4 replicates of HA+ ATII and 4 replicates of HA+ CC isolated from the lung lobes of IRF3/7-/- mice on 9 h p.i. with PR8. 4 replicates of mock-infected (HA-) ATII and 4 replicates of mock-infected (HA-) CC isolated from the lung lobes of mock-infected IRF3/7-/- mice on 9 h p.i. with allantoic fluid of equal dilution as PR8.
Publication Title
Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus Infection <i>Ex Vivo</i>.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors
Publication Title
Granzyme B expression is enhanced in human monocytes by TLR8 agonists and contributes to antibody-dependent cellular cytotoxicity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There are currently no biological tests that differentiate patients with bipolar disorder (BPD) from healthy controls. While there is evidence that peripheral gene expression differences between patients and controls can be utilized as biomarkers for psychiatric illness, it is unclear whether current use or residual effects of antipsychotic and mood stabilizer medication drives much of the differential transcription. We therefore tested whether expression changes in first-episode, never-medicated bipolar patients, can contribute to a biological classifier that is less influenced by medication and could potentially form a practicable biomarker assay for BPD.
Publication Title
Utilization of never-medicated bipolar disorder patients towards development and validation of a peripheral biomarker profile.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We are examining the genes that control initiation and progression of murine medulloblastomas that result from loss of patched. Approximately 25% of human medulloblastomas have mutations in patched or in other elements of the sonic hedgehog pathway. However, the cells from which these tumors originate (neural progenitors or stem cells), the cells that are responsible for tumor propagation (cancer stem cells), and the genes that are required for tumor progression are poorly understood. To address these questions, we have developed conditional patched knockout mice in which the gene is deleted in neural stem cells or progenitors. In addition, we have isolated a population of tumor-propagating cells from these tumors. By studying these models we will gain insight into the mechanisms of tumorigenesis and identify new targets for therapy.
Publication Title
Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples