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GSE48217
Mus musculus
41 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The 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.
Publication Title
Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus, Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene transcription effects of mutations in the infuenza virus A/Hong Kong/1/1968(H3N2) nonstructural 1 NS1 gene in infected human A549 (lung epithilium) cells
Publication Title
Influenza A/Hong Kong/156/1997(H5N1) virus NS1 gene mutations F103L and M106I both increase IFN antagonism, virulence and cytoplasmic localization but differ in binding to RIG-I and CPSF30.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Cytochrome P450 aromatase is an essential enzyme for vertebrates. It is responsible for the conversion of androgens to estrogens in the brain and gonadal tissues. Aromatase converts testosterone into estradiol and therefore participates in the regulation of many processes which are controlled by estrogens such as development and fertility. Teleosts have been characterized as having exceptionally high levels of brain estrogen biosynthesis when compared to the brains of the other vertebrates. Little is known about the effects of estrogens on brain function in teleosts. The main objective of this study was to assess the effects of fadrozole, a powerful aromatase inhibitor, on gene expression in the zebrafish brain. To achieve this, male zebrafish were exposed to fadrozole for 10 days. This exposure causes a decrease in estrogens along with an increase in androgens. Plasma testosterone levels showed a 3-fold increase in response to the exposure. In the telencephalon, 235 genes were identified by Affymetrix GeneChip analysis as being differentially regulated. Real-time RT-PCR was used to validate the data obtained from the microarrays. This technique was also used to evaluate the response in the hypothalamus, which appears to follow similar transcriptional regulation. Gene ontology analysis of the microarray data revealed common biological processes and molecular functions such as sensory perception and detection of light stimulus, homeobox and transcription factor complexes. This study has identified genes which are directly and/or indirectly controlled by estrogens and androgens which helped to demonstrate the pronounced effects of endocrine disrupting chemicals on gene expression in the brain of teleosts. Collectively, the results provide a better understanding of the effects of aromatase inhibitors on gene expression and also shed light on the underlying effects of sex hormone variation and their importance in the brain of teleosts.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
PGC-1s (PGC-1alpha and PGC-1beta) are transcriptional coactivators involved in mitochondrial biogenesis, metabolism, and antioxidant defense. Given the existing links between PGC-1s and aging, we wanted to investigate the contribution of PGC-1s to skin aging. Keratinocytes form a self-renewable layer that differentiate to generate full epidermis. Defects in keratinocyte metabolism related to aging or PGC-1s depletion could impair normal function of keratinocytes and contribute to skin thinning.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Despite its high prevalence and economic burden, the etiology of human hypertension remains incompletely understood. Here we identify the transcription factor Gata5, as a new gene involved in regulation of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells (mEC) and its genetic inactivation in mice leads to hypertension, vascular endothelial dysfunction and renal inflammation. Aged Gata5-Null mice develop salt-sensitivity and target-organ damage reminiscent of the progression of human hypertension. Endothelial-specific inactivation of Gata5 increases BP and leads to vascular endothelial dysfunction, confirming the endothelial component of Gata5 inactivation-related hypertension. To directly assess the effect of loss of GATA5 on endothelial cells, we generated a stable GATA5 knockdown cell line (HDMEC-Gata5KO) by infecting human dermal microvascular endothelial cells with a lentiviral vector containing an anti-Gata5 shRNA followed by a transcriptomic analysis. The control cells were infected with a lentivirus containing an empty vector pLKO2.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Our lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line spontaneously transformed into the spontaneously transformed OSE (STOSE) cell line in mid 2012.
Publication Title
A new spontaneously transformed syngeneic model of high-grade serous ovarian cancer with a tumor-initiating cell population.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Our lab established the M0505 cell line from the ovarian surface epithelium (OSE) of FVB/N mice in May 2005 in order to study OSE biology. This cell line was infected with PAX2 to study the biological consequences of PAX2 expression in normal mOSE cells
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse cortex (dorsal telencephalon) analysis from Snf2h cKO-Emx1 mice versus control littermates at birth (P0).
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. We have previously established that bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA. Profiling the transcriptomes of ES cells differentiated with bexarotene or RA permits the identification of different genetic targets and signaling pathways that may contribute to the difference of bexarotene and RA in efficiency of myogenesis. Interestingly, bexarotene induces the early expression of a myogenic progenitor marker, Meox1, while the expression of many RA targets is also enhanced by bexarotene. Several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and RA, suggesting that early targets of rexinoids allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in ES cells.
Publication Title
Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Our work demonstrated that miR-183 cluster regulates IFN production and signaling
Publication Title
A conserved miRNA-183 cluster regulates the innate antiviral response.
Sample Metadata Fields
Cell line
View Samples