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SRP092552
Mus musculus
86 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington’s disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models and PDE10 loss may represent a homeostatic adaptation to maintain signaling. Elevation of both cAMP and cGMP by PDE10 inhibition were required for rescue. Phosphoproteomic profiling of striatum in response to PDE10 inhibition highlighted plausible neural substrates responsible for the improvement. Early chronic PDE10 inhibition in Q175 mice showed improvements beyond those seen with acute administration after symptom onset, including partial reversal of striatal deregulated transcripts and the prevention of the emergence of HD neurophysiological deficits. Overall design: Transcriptional profiling of cortex and striatal tissue following chronic dosing of either vehicle or the PDE10A inhibitor PF-02545920 (0.32, 1 and 3.2 mg/kg po qd) in the Q175 homozygous knock-in mouse model of Huntington’s disease (dosing from 5-weeks to 9 months of age).
Publication Title
Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington's Disease Models.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of gene expression data in two C.elegans mutant strains: KP3293 tom-1(nu468) and KP3365 unc-43(n1186); hif-1(nu469). These results support the utility of microarray hybridizations to facilitate positional cloning.
Publication Title
Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Exon expression profiling was performed on 37 clinical DLBCL samples and subsequently analyzed using alternative splice analysis of vairance (asANOVA) implemented in Partek Genomics Suite in order to identify alternative spliced genes.
Publication Title
Expression of NOTCH3 exon 16 differentiates Diffuse Large B-cell Lymphoma into molecular subtypes and is associated with prognosis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of the study was to investigate the activation of human NK cells by IL2 through analyzing the global gene expression at different time points (0, 2, 8 and 24 hours) after culture with the cytokine IL2 at 100 IU/ml. NK cells with the CD56+/CD16+ and CD3- phenotype were negatively selected by immunomagnetic beads and re-examined by flow-cytometry to ensure greater than 90% purity .
Publication Title
Genome wide transcriptional analysis of resting and IL2 activated human natural killer cells: gene expression signatures indicative of novel molecular signaling pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_18.0 (huex10st)
Description
Mononuclear cells were isolated from the sternal bone marrow and prepared for multiparametric flow cytometry using an optimized and validated protocol. B-cell subsets of PreBI, PreBII, Immature, Naive, Memory and Plasma cells were isolated and a al of 38 gene expression profiles were generated using the HuEx-1_0-st-v2-micro array chip from Affymetrix to characterize the gene expression in the individual subpopulations.
Publication Title
Long Noncoding RNA Expression during Human B-Cell Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_18.0 (huex10st)
Description
Long noncoding RNAs (lncRNAs) have emerged as important regulators of diverse cellular processes, but their roles in the developing immune system are poorly understood. In this study, we analysed lncRNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies (n=7), and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples (n=6), respectively. A remapping strategy was used to assign the array probes to 37630 gene-level probe sets, reflecting the most recent updates in genomic and transcriptomic databases, which enabled expression profiling of 19579 long noncoding RNAs, comprising 3947 antisense RNAs, 5277 lincRNAs, 7625 pseudogenes, and 2730 additional lncRNAs. As a first step towards inferring the functions of the identified lncRNAs in developing B-cells, we analysed their co-expression with well-characterized protein-coding genes, a method known as guilt by association. By using weighted gene co-expression network analysis, we identified 272 lincRNAs, 471 antisense RNAs, 376 pseudogene RNAs, and 64 lncRNAs within seven sub-networks associated with distinct stages of B-cell development, such as early B-cell development, B-cell proliferation, affinity maturation of antibody, and terminal differentiation. These data provide an important resource for future studies on the functions of lncRNAs in development of the adaptive immune response, and the pathogenesis of B-cell malignancies that originate from distinct B-cell subpopulations.
Publication Title
Long Noncoding RNA Expression during Human B-Cell Development.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A predictive gene list for response to high dose melphalan therapy in patients diagnosed with multiple myeloma is generated by combining results from dose response experiments and microarray data using a B-cell line panel and the introduction of multivariate regression techniques.
Publication Title
Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used global gene expression profiles from human B-cell cell lines to generate gene expression signatures for prediction of response to the drugs cyclophosphamide, doxorubicin or vincristine. The signatures were validated in two publicly available clinical cohorts.
Publication Title
Predicting response to multidrug regimens in cancer patients using cell line experiments and regularised regression models.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
The purpose of this study was to develop a quantification method that can be used to assess the ability of tag-seq to detect malignant B-cell transcripts. The data support that tumour cell concentration is an important variable with fundamental impact on gene expression pattern. Overall design: We analysed eight serial dilutions of the malignant B-cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293, by tag-sequencing. No technical replicates were performed.
Publication Title
A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.
Sample Metadata Fields
Cell line, Subject
View Samples