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GSE56449
Homo sapiens
30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PAX5-JAK2 has recently been identified as a novel recurrent fusion gene in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) but the function of the encoded chimeric protein has not yet been characterized in detail. Herein we show that the PAX5-JAK2 chimera, which consists of the DNA-binding paired domain of PAX5 and the active kinase domain of JAK2, is a nuclear protein that has the ability to bind to wild-type PAX5 target loci. Moreover, our data provide compelling evidence that PAX5-JAK2 functions as nuclear catalytically active kinase that autophosphorylates and in turn phosphorylates and activates downstream STATs in an apparently non-canonical mode. The chimeric protein also enables cytokine-independent growth of Ba/F3 cells and, therefore, possessing transforming potential. Importantly, the kinase activity of PAX5-JAK2 can be efficiently blocked by JAK2 inhibitors rendering it a potential target for therapeutic intervention. Together, our data show that PAX5-JAK2 simultaneously deregulates the PAX5 downstream transcriptional program and activates the JAK-STAT signaling cascade, and thus, by interfering with these two important pathways, may promote leukemogenesis.
Publication Title
The role of the Janus-faced transcription factor PAX5-JAK2 in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
In this work we present the PrPC-dependent gene expression signature in N2A cells and its implication on the most overrepresented functions; cell cycle, cell growth and proliferation and cell morphology.
Publication Title
PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiSeq2000
Description
Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNa2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNa2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNß also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response. Overall design: HuH7 cells were treated with 10000 units/ml of IFN a2 and RNA was isolated 3 days post-treatment
Publication Title
Type I Interferon Regulates the Expression of Long Non-Coding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Rheumatoid arthritis is an autoimmune disease in which joint inflammation lead to progressive cartilage and bone destruction. Matrix metalloproteinases (MMP) implicated in homeostasis of extracellular matrix (ECM) play a central role in cartilage degradation. The aim of this study was to investigate the role of MMP-8 (collagenase-2) suppression in the K/BxN serum-transfer arthritis model.
Publication Title
Matrix metalloproteinase-8 deficiency increases joint inflammation and bone erosion in the K/BxN serum-transfer arthritis model.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The aim of this study is to identify genes implicated in the early steps of the autoimmune process, prior to inflammation in type 1 diabetes. Early Insulin AutoAntibodies (E-IAA) have been used as subphenotypic marker to select individual animals as type 1 diabetes prone and to compare gene expression patterns with insulin autoantibody negative NOD.
Publication Title
Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HiSeq 2500
Description
BACKGROUND: We characterized the whole transcriptome of circulating tumor cells (CTCs) in Stage II-III breast cancer to evaluate correlations with primary tumor biology. METHODS: CTCs were isolated from peripheral blood (PB) via immunomagnetic enrichment followed by fluorescence-activated cell sorting (IE-FACS). CTCs, PB and fresh tumors were profiled with RNA Seq. Formalin-fixed, paraffin-embedded (FFPE) tumors were subjected to RNA Seq and NanoString PAM50 assays with Risk of Recurrence (ROR) scores. RESULTS: CTCs were detected in 29/33 (88%) of patients. We selected 21 cases to attempt RNA Seq (median number of CTCs=9). 16 CTC samples yielded results that passed quality control metrics. These samples had a median of 4,311,255 uniquely mapped reads, less than PB or tumors. Intrinsic subtype predicted by comparing estrogen receptor (ER), progesterone receptor (PR) and HER2 versus PAM50 for FFPE tumors was 85% concordant. However, CTC RNA Seq subtype assessed by the PAM50 classification genes was highly discordant both with the subtype predicted by ER/PR/HER2 as well as by tumor PAM50. Two patients died of metastatic disease - both had high ROR scores and high CTC counts. We identified significant genes, canonical pathways, upstream regulators and molecular interaction networks comparing CTCs by various clinical factors. We identified a 75-gene signature with highest expression in CTCs and tumors taken together that was prognostic in The Cancer Genome Atlas and METABRIC datasets. CONCLUSION: It is feasible to use RNA Seq of CTCs in non-metastatic patients to discover novel tumor biology characteristics. Overall design: 6 peripheral blood samples from healthy individuals (negative controls) were compared to circulating tumor cells from n=16 patients, with comparison to the primary tumors available for n=12 of these patients
Publication Title
RNA-Seq of Circulating Tumor Cells in Stage II-III Breast Cancer.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
three replicates of HT29 cells per conditionwere grown under normoxic and hypoxic conditions. RNA and miRNA was extracted from each replicate and run on the GPL570 and GPL5106 arrays respectively.
Publication Title
Role of oxygen availability in CFTR expression and function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Eptstein-Barr Virus, an oncogenic herpesvirus, infects and immortalizes human B cells in culture into indefinitely-proliferating LCLs. We examined the gene expression of primary B cells during the process of infection and growth transformation at the exon level to analyze early and late virus-induced changes in expression and exon usage.
Publication Title
An ATM/Chk2-mediated DNA damage-responsive signaling pathway suppresses Epstein-Barr virus transformation of primary human B cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We aimed at analyzing the transcriptome changes associated with the deletion of a portion of the Alu element from MIR205HG transcript
Publication Title
LEADeR role of miR-205 host gene as long noncoding RNA in prostate basal cell differentiation.
Sample Metadata Fields
Cell line
View Samples