RNA sequencing was used to explore global gene expression in the chronic relapsing and secondary progressive EAE (pEAE) Biozzi ABH mouse model of MS. Spinal cord tissue RNA from pEAE Biozzi ABH mice and healthy littermate controls was sequenced. 2,072 genes were differentially expressed (q<0.05) from which 1,397 were significantly upregulated and 675 were significantly downregulated. This hypothesis-free investigation characterised the genomic changes that describe the pEAE mouse model. Overall design: Examination of 3 control and 3 pEAE mice
Characterisation of Transcriptional Changes in the Spinal Cord of the Progressive Experimental Autoimmune Encephalomyelitis Biozzi ABH Mouse Model by RNA Sequencing.
Specimen part, Subject
View SamplesThe abstract of the associated publication (Selga E, No V, Ciudad CJ. Biochemical Pharmacology, 2008) is the following:
Transcriptional regulation of aldo-keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis.
No sample metadata fields
View SamplesOur data demonstrate that overexpression of the polarity protein Crb3 elicits changes in MCF-10A cells that culminate in an increase in the release of amphiregulin (AR) and the subsequent activation of EGFR signaling to drive proliferation. Microarray analysis was performed to define global changes in the transcriptional landscape induced by Crb3. Results provide insight into a FERM domain protein (EBP41L4B) required for Crb3 mediated induction of proliferation.
CRB3 and the FERM protein EPB41L4B regulate proliferation of mammary epithelial cells through the release of amphiregulin.
Cell line, Treatment
View SamplesWe have observed that follicular B cells from mice with a hypomorphic mutation (IkL/L) in the Ikzf1 gene (which encodes the Ikaros transcription factor) exhibit an increased proliferative response to anti-IgM stimulation (Kirstetter et al, Eur J Immunol, 32:720-30, 2002). We asked if Ikaros controls the transcriptional response that unfolds after activation, or if differences in the transcriptional landscape of resting B cells could explain the altered response. To this end, we have determined the transcriptome of unstimulated WT and IkL/L follicular B cells, as well as that of cells stimulated for 3h and 12h with anti-IgM. Samples from 2 independent experients were analyzed.
Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways.
Age, Specimen part
View SamplesKnockdowns of c-JUN and JUND had opposite effects on PC3 prostate cell migration. We predicted that c-JUN and JUND control the same set of cell migration genes, but in opposite directions. To test this hypothesis, mRNA with expression changes in c-JUN and JUND knockdown PC3 cell lines were compared to mRNA levels in control (luciferase knockdown) PC3 cells by RNA-seq. Overall design: mRNA profiles of luciferase knockdown (WT), c-Jun knockdown, and Jun-D knockdown in PC3 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.
No sample metadata fields
View SamplesA summary of the work associated to these microarrays is the following:
Role of caveolin 1, E-cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Networking of differentially expressed genes in human cancer cells resistant to methotrexate.
Specimen part, Cell line
View SamplesThe NS1 protein of influenza A virus (IAV) is a multifunctional virulence factor. Mouse adaptive mutations in the NS1 protein of the human isolate A/Hong Kong/1/1968(H3N2) (HK) have been previously reported to increase virulence, viral fitness, and interferon antagonism, but differ in binding to post-transcriptional processing factor CPSF30. Because nuclear trafficking is a major genetic determinant of influenza virus host adaptation, we assessed subcellular localization and host gene expression of NS1 adaptive mutations. Recombinant HK viruses with adaptive mutations in the NS1 gene were assessed for NS1 protein subcellular localization in mouse and human cells using confocal microscopy and cellular fractionation. HK-wt virus NS1 partitioned equivalently between the cytoplasm and nucleus in human cells but was defective in cytoplasmic localization in mouse cells. The adaptive mutations either increased the proportion or abundance of NS1 in the cytoplasm, and/or the nucleus. NS1 mutations that increased cytoplasmic distribution identified a putative second nuclear export signal (NES) spanning aa positions 98-106 LSEDWFMLM, (mutation sites in bold); with the strongest effect seen for mutation M106I. The putative NES in the NS3 protein was associated with cytoplasmic localization. The host gene expression profile of the adaptive mutants was determined by microarray analysis of infected mouse cells to show either high or low gene regulation (HGR or LGR) phenotypes that mapped to the amino-terminal and the carboxy-terminal regions respectively. The HGR and LGR mutations were predominantly down regulating versus up regulating respectively. The greatest effect on host gene expression in the HGR group correlated with the ability of the NS1 protein to bind CPSF30. To our knowledge this is the first report of roles of adaptive NS1 mutations that affect intracellular localization and regulation of host gene expression.
Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.
Specimen part, Cell line
View SamplesGDF5 is a potent tenogenic differentiation inducer. We previously demonstrated that GDF5 induced in vitro tenogenesis of human bone marrow-derived stromal cells (hMSC).
Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells.
Specimen part, Subject
View SamplesInherited genetic risk factors play an important role in cancer. However, other than cancer susceptibility genes found in familial cancer syndromes and inherited in a Mendelian fashion, little is known about modifier genes (germline variants that interact with each other and with environmental factors) that contribute to individual susceptibility. Here we develop a strategy parental strain expression mapping (PSEM), which utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses, to directly identify candidate germline modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. In keeping with findings in murine models, the expression of the glycolysis pathway was strongly enriched in the non-cancer prostate tissue from patients with prostate cancer who did not recur after surgical resection. Together these data suggest that PSEM can directly identify germline modifier pathways of relevance to human disease.
Identification of prostate cancer modifier pathways using parental strain expression mapping.
Age
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