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GSE79341
Homo sapiens
3 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hepatitis C virus (HCV)-induced chronic liver disease is one of the leading causes of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCC development following chronic HCV infection remain poorly understood. MicroRNAs (miRNAs) play an important role in cellular homeostasis within the liver and deregulation of the miRNome has been associated with liver disease including HCC. While host miRNAs are essential for HCV replication, viral infection in turn appears to induce alterations of intrahepatic miRNA networks. Although the cross-talk between HCV and liver cell miRNAs most likely contributes to liver disease pathogenesis, the functional involvement of miRNAs in HCV-driven hepatocyte injury and HCC remains elusive. Here, we combined a hepatocyte-like based model system, high-throughput small RNA-sequencing, computational analysis and functional studies to investigate HCV-miRNA interactions that may contribute to liver disease and HCC. Profiling analyses indicated that HCV infection differentially regulated the expression of 72 miRNAs by at least two-fold including miRNAs that were previously described to target genes associated with inflammation, fibrosis and cancer development. Further investigation demonstrated that miR-146a-5p was consistently increased in HCV-infected hepatocyte-like cells and primary human hepatocytes as well as in liver tissues from HCV-infected patients. Genome-wide microarray and computational analyses indicated that miR-146a-5p over-expression is related to liver disease and HCC development. Furthermore, we showed that miR-146a-5p positively impacts on late steps of the viral replication cycle thereby increasing HCV infection. Collectively, our data indicate that the HCV-induced increase in miR-146a-5p expression both promotes viral infection and is relevant for pathogenesis of liver disease.
Publication Title
Hepatitis C Virus-Induced Upregulation of MicroRNA miR-146a-5p in Hepatocytes Promotes Viral Infection and Deregulates Metabolic Pathways Associated with Liver Disease Pathogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Publication Title
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We used microarray analysis to investigate if keratinocytes excert an immuno-inflammatory response towards streptococcal M1 protein.
Publication Title
Vigilant keratinocytes trigger pathogen-associated molecular pattern signaling in response to streptococcal M1 protein.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We used the flu mutant of Arabidopsis and a transgenic line that overexpresses the thylakoid-bound ascorbate peroxidase (tAPX) to address the interactions between different reactive oxygen species (ROS) signaling pathways. 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 (1O2). Immediately 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 (H2O2), suggesting that different types of active oxygen species activate distinct signaling pathways. It was not known whether the pathways operate separately or interact with each other. We have addressed this problem by modulating noninvasively the level of H2O2 in plastids by means of a transgenic line that overexpresses the thylakoid-bound ascorbate peroxidase (tAPX, line 14/2 PMID: 15165186). In the flu mutant overexpressing tAPX, the expression of most of the nuclear genes that were rapidly activated after the release of 1O2 was significantly higher in flu plants overexpressing tAPX, whereas in wild-type plants, overexpression of tAPX had only a very minor impact on nuclear gene expression. The results suggest that H2O2 antagonizes the 1O2-mediated signaling of stress responses as seen in the flu mutant. This cross-talk between H2O2- and 1O2-dependent signaling pathways might contribute to the overall stability and robustness of wild-type plants exposed to adverse environmental stress conditions.
Publication Title
Cross-talk between singlet oxygen- and hydrogen peroxide-dependent signaling of stress responses in Arabidopsis thaliana.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 29 Downloadable Samples
Illumina HiSeq 2500
Description
Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus [lipopolysaccharide (LPS) or saline], and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change = 2 and FDR = 0.05) in the broiler (N=283) than the Fayoumi (N=85), whereas heat treatment resulted in fewer DEG in broiler (N=22) compared to Fayoumi (N=107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. Overall design: At 22 days of age, divergent chicken breeds (Fayoumi and broiler) were treated with a thermal treatment (heat stress at 35C, or thermoneutral at 25C as a control) for 3.5 hours, then stimulated subcutaneously with an inflammatory stimulus (LPS, or saline as a control) for another 3.5 hours. Chickens were euthanized and spleens were harvested. A total of 32 indivudally coded cDNA libraries were prepared using TruSeq v2 library preparation kit which selects for polyA mRNA. In this 2x2x2 full factorial design with the factors of breed, thermal treatment, and inflammatory stimulus, there were a total of 8 treatment groups. Each treatment group had a total of 4 animal biological replicates. Therefore, a total of 32 individual barcoded samples were sequenced. A total of 8 individually barcoded cDNA libraries were sequenced per lane using the HiSeq Illumina 2500, and we used 4 lanes total. Reads were mapped to Galgal 2.0.
Publication Title
Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The goals of the microarray experiment were to determine the role of MAF1, the Toxoplasma gondii mediator of host mitochondrial association, on host cell gene expression by comparing infection of WT cells with Type II and Type II:MAF1 parasites. We also explored the role of MAF1 on host cell gene expression by comparing profiles of WT and MAVS KO MEFs infected with Type I and Type Imaf1KO parasites.
Publication Title
Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A fundamental question in developmental biology is whether there are mechanisms to detect stem cells with mutations that, although not adversely affecting viability, would compromise their ability to contribute to further development. Here, we show that cell competition is a mechanism regulating the fitness of embryonic stem cells (ESCs). We find that ESCs displaying defective bone morphogenetic protein signaling or defective autophagy or that are tetraploid are eliminated at the onset of differentiation by wild-type cells. This elimination occurs in an apoptosis-dependent manner and is mediated by secreted factors. Furthermore, during this process, we find that establishment of differential c-Myc levels is critical and that c-Myc overexpression is sufficient to induce competitive behavior in ESCs. Cell competition is, therefore, a process that allows recognition and elimination of defective cells during the early stages of development and is likely to play important roles in tissue homeostasis and stem cell maintenance.
Publication Title
Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
T lymphocytes can be generated from T-cell-derived induced pluripotent stem cells (T-iPS). We used microarrays to better elucidate their phenotype and compare their gene expression profile to that of known lymhoid subsets from peripheral blood.
Publication Title
Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A fundamental question in developmental biology is whether there are mechanisms to detect stem cells with mutations that although do not adversely affect their viability, would compromise their ability to contribute to further development. Here we show that cell competition is a novel mechanism regulating the fitness of embryonic stem cells (ESCs). We find that ESCs displaying defective BMP signalling, defective autophagy or are tetraploid are eliminated at the onset of differentiation by wild-type cells. This elimination occurs in an apoptotic dependent manner and is mediated by secreted factors. Furthermore, during this process we find that establishment of differential cMyc levels is critical and that cMyc over-expression is sufficient to induce competitive behaviour in ESCs. Cell competition is therefore a process that allows recognition and elimination of defective cells during the early stages of development and is likely to play important roles in tissue homeostasis and stem cell maintenance.
Publication Title
Competitive interactions eliminate unfit embryonic stem cells at the onset of differentiation.
Sample Metadata Fields
Specimen part
View Samples