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SRP007941
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer II
Description
OBJECTIVE: MicroRNAs (miRNAs, miRs), a class of small non-coding RNA molecules, are posttranscriptional regulators involved in a plethora of cellular functions and have been proposed as potential therapeutic targets in various diseases, including rheumatoid arthritis (RA). In this study, we sought to discover novel miR associations in synovial fibroblasts (SFs), a key cell type mediating RA pathogenesis, by performing miR expression profiling on cells isolated from the human TNF transgenic mouse model (TghuTNF or Tg197). METHODS: miR expression in SFs isolated from 8-week-old, fully diseased TghuTNF and WT littermate control mice were determined by deep sequencing of small RNAs and the arthritic profile was established by pairwise comparisons of the two groups. qRT-PCR analysis was utilised for profile validation purposes and miR quantitation in patient SFs. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms. Overall design: Synovial Fibroblasts isolated from TghuTNF mice (2 x biological replicates) and control WT littermate mice (2 x biological replicates)
Publication Title
Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 78 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative splicing of pre-mRNA is a mechanism that increases the protein diversity of a single gene by differential exon inclusion during post-transcriptional processing. While alternative splicing is established to occur during lymphocyte activation, little is known about the role it plays during the immune response. Our study is among the first reports of a systematic genome-wide analysis using whole exon DNA microarrays integrating alternative splicing and differential gene expression. Purified human CD2+ T or CD19+ B cells were activated using protocols to model the early events in post-transplant allograft immunity and sampled as a function of time during the process of immune activation. Here we show that 3 distinct classes of alternatively spliced and/or differentially expressed genes change in an ordered manner as a function of immune activation. We mapped our results to function-based canonical pathways and demonstrated that some are populated by only one class of genes, like integrin signaling, while other pathways, such as purine metabolism and T cell receptor signaling, are populated by all three classes of genes. Our studies augment the current view of T and B cell activation in immunity that has been based exclusively upon differential gene expression by providing evidence for a large number of molecular networks populated as a function of time and activation by alternatively spliced genes, many of which are constitutively expressed.
Publication Title
Genome-wide analysis of immune activation in human T and B cells reveals distinct classes of alternatively spliced genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Expression levels of retinoic acid receptor gamma (NR1B3/RARG, encodes RARG), are commonly reduced in prostate cancer (PCa). Therefore we sought to establish the cellular and gene regulatory consequences of reduced RARG expression, and determine RARG regulatory mechanisms. RARG shRNA approaches in non-malignant (RWPE-1 and HPr1-AR) and malignant (LNCaP) prostate models revealed that reducing RARG levels, rather than adding exogenous retinoid ligand, had the greatest impact on prostate cell viability and gene expression. ChIP-Seq defined the RARG cistrome which was significantly enriched at active enhancers associated with AR binding sites. Reflecting a significant genomic role for RARG to regulate androgen signaling, RARG knockdown in HPr1-AR cells significantly regulated the magnitude of the AR transcriptome. RARG down-regulation was explained by increased miR-96 in PCa cell and mouse models, and TCGA PCa cohorts. Biochemical approaches confirmed that miR-96 directly regulated RARG expression and function. Capture of the miR-96 targetome by biotin-miR96 identified that RARG and a number of RARG interacting co-factors including TACC1 were all targeted by miR-96, and expression of these genes were prominently altered, positively and negatively, in the TCGA-PRAD cohort. Differential gene expression analyses between tumors in the TCGA-PRAD cohort with lower quartile expression levels of RARG and TACC1 and upper quartile miR-96, compared to the reverse, identified a gene network including several RARG target genes (e.g. SOX15) that significantly associated with worse disease free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p=0.015). In summary, miR-96 targets a RARG network to govern AR signaling, PCa progression and disease outcome.
Publication Title
The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Expression levels of retinoic acid receptor gamma (NR1B3/RARG, encodes RARG), are commonly reduced in prostate cancer (PCa). Therefore we sought to establish the cellular and gene regulatory consequences of reduced RARG expression, and determine RARG regulatory mechanisms. RARG shRNA approaches in non-malignant (RWPE-1 and HPr1-AR) and malignant (LNCaP) prostate models revealed that reducing RARG levels, rather than adding exogenous retinoid ligand, had the greatest impact on prostate cell viability and gene expression. ChIP-Seq defined the RARG cistrome which was significantly enriched at active enhancers associated with AR binding sites. Reflecting a significant genomic role for RARG to regulate androgen signaling, RARG knockdown in HPr1-AR cells significantly regulated the magnitude of the AR transcriptome. RARG down-regulation was explained by increased miR-96 in PCa cell and mouse models, and TCGA PCa cohorts. Biochemical approaches confirmed that miR-96 directly regulated RARG expression and function. Capture of the miR-96 targetome by biotin-miR96 identified that RARG and a number of RARG interacting co-factors including TACC1 were all targeted by miR-96, and expression of these genes were prominently altered, positively and negatively, in the TCGA-PRAD cohort. Differential gene expression analyses between tumors in the TCGA-PRAD cohort with lower quartile expression levels of RARG and TACC1 and upper quartile miR-96, compared to the reverse, identified a gene network including several RARG target genes (e.g. SOX15) that significantly associated with worse disease free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p=0.015). In summary, miR-96 targets a RARG network to govern AR signaling, PCa progression and disease outcome.
Publication Title
The miR-96 and RARγ signaling axis governs androgen signaling and prostate cancer progression.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used the flu mutant of Arabidopsis to detail gene expression in response to singlet oxygen. The conditional flu mutant of Arabidopsis accumulates excess protochlorophyllide in the dark within chloroplast membranes that upon illumination acts as a photosensitizer and generates singlet oxygen. Immediately after the release of singlet oxygen mature flu plants stop growing, whereas seedlings bleach and die. Within the first 30 min after the release of singlet oxygen rapid changes in nuclear gene expression occur. Distinct sets of genes were activated that were different from those induced by other reactive oxygen species, superoxide or hydrogen peroxide.
Publication Title
Rapid induction of distinct stress responses after the release of singlet oxygen in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used microarrays to detail Arabidopsis gene expression in response to paraquat, a herbicide that acts as a terminal oxidant of photosystem I that in the light leads to the enhanced generation of superoxide and hydrogen peroxide inside plastids. Within a few hours after paraquat treatment changes in nuclear gene expression occur. Distinct sets of genes were activated that were different from those induced by another reactive oxygen species, singlet oxygen.
Publication Title
Rapid induction of distinct stress responses after the release of singlet oxygen in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 179 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we employed transcriptome mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response. The flow cytometry data confirms depletion of specific cell subsets in response to ATG induction and immunosuppression with sustained decreases in CD4 as well as CD8 cell subsets. A series of T cell activation markers were expressed from Pre-Tx to 12 weeks indicating the evolution of immunity including expansion of CD45RO+CD62L- effector memory cells. Serial whole blood transcript monitoring demonstrated over 2000 differentially expressed genes, with over 80 percent down-regulated Post-Tx. However, cell subset analysis revealed a unique spectrum of subset-specific gene expression with time-dependent changes, with contrasting significant Post-Tx gene upregulation. Our results provide a unique view of the complex evolution of immune/inflammatory molecular networks marking the early post transplant immune response. A critical finding is that analysis of the constituent blood cell subsets provides an entirely new level of detail revealing the nature of this process, effectively deconvoluting the changes that are otherwise lost in the noise of cellular complexity of whole blood.
Publication Title
Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 268 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
RNA was isolated from bronchial brushings obtained from current and former smokers with and without COPD. mRNA expression was profiled using Affymetrix Human Gene 1.0 ST Arrays.
Publication Title
A dynamic bronchial airway gene expression signature of chronic obstructive pulmonary disease and lung function impairment.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 100 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples