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GSE100928
Homo sapiens
30 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Type I interferons (IFN) are important components of the innate antiviral response. A key signalling pathway activated by IFNa is the Janus kinase signal transducer and activator of transcription (JAKSTAT) pathway. Major components of the pathway have been identified. However, critical kinetic properties that facilitate accelerated initiation of intracellular antiviral signalling and thereby promote virus elimination remain to be determined. By combining mathematical modelling with experimental analysis, we show that control of dynamic behaviour is not distributed among several pathway components but can be primarily attributed to interferon regulatory factor 9 (IRF9), constituting a positive feedback loop. Model simulations revealed that increasing the initial IRF9 concentration reduced the time to peak, increased the amplitude and enhanced termina- tion of pathway activation. These model predictions were experimentally verified by IRF9 over-expression studies. Furthermore, acceleration of signal processing was linked to more rapid and enhanced expression of IFNa target genes. Thus, the amount of cellular IRF9 is a crucial determinant for amplification of early dynamics of IFNa-mediated signal transduction.
Publication Title
Combining theoretical analysis and experimental data generation reveals IRF9 as a crucial factor for accelerating interferon α-induced early antiviral signalling.
Sample Metadata Fields
Specimen part, Disease, Cell line, Time
View Samples- Mus musculus, Homo sapiens
- 23 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.
Publication Title
VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Leukemia Inhibitory Factor is an important cytokine of the IL family. Recent findings suggest it has a crucial role in cancer progression
Publication Title
Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 1 Downloadable Sample
Illumina Genome Analyzer II
Description
Although the locations of promoters and enhancers have been identified in several cell types, we have yet limited information on their connectivity. We developed HiCap, which combines Hi-C with promoter sequence capture, to enable genome-wide identification of regulatory interactions with single-enhancer resolution. HiCap analyses of mouse embryonic stem cells (mESC) identified promoter-enhancer interactions predictive of gene expression change upon perturbation, opening up for genomic analyses of long-range gene regulation. Overall design: HiCap was designed by combining Hi-C with with sequence capture (for all promoters) and carried out in mouse embryonic stem cells (mESC)
Publication Title
Genome-wide mapping of promoter-anchored interactions with close to single-enhancer resolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
A study on the effects of an sdiA mutant and the AHL molecule on the virulence of EHEC
Publication Title
Chemical sensing in mammalian host-bacterial commensal associations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Background: Interaction between key signaling mechanisms is important to generate the diversity in signaling output required for proper control of cellular differentiation and function, although the molecular manifestations of such cross-talk are only partially understood. Notch signaling and the cellular response to hypoxia intersect at different points in the signaling cascades, and in this report we analyze the consequences of this cross-talk at the transcriptome level. Results: Mouse ES cells were subjected to various combinations of hypoxia and/or activated Notch signaling, and the transcriptome changes could be grouped into different categories, reflecting various modes of hypoxia and Notch signaling integration. Two principal categories of novel Notch- and hypoxia-induced genes were identified: i) a larger set of genes induced by one pathway and not significantly affected by the activity status of the other pathway; and ii) a smaller set of genes co-regulated by Notch and hypoxia. In the latter category, we identified genes that were induced by hypoxia and the expression of which was enhanced by active Notch signaling. In addition, a number of genes were induced by Notch and hypoxia independently, and a final category of genes required simultaneous activation of Notch and hypoxia to be significantly induced. Several of the hypoxia- and Notch-induced genes were found to be upregulated in various forms of cancer. Conclusions: We identify novel Notch and hypoxia downstream genes and genes co-regulated by the two pathways, providing a molecular platform to better understand the intersection between the two signaling cascades in normal development and cancer.
Publication Title
Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem cells.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Hyperactivation of Notch signaling and the cellular hypoxic response are frequently observed in cancers, with increasing reports of connections to tumor initiation and progression. The two signaling mechanisms are known to intersect, but while it is well established that hypoxia regulates Notch signaling, less is known about whether Notch can regulate the cellular hypoxic response. We now report that Notch signaling specifically controls expression of HIF2a, a key mediator of the cellular hypoxic response. Transcriptional upregulation of HIF2a by Notch under normoxic conditions leads to elevated HIF2a protein levels in primary breast cancer cells as well as in human breast cancer, medulloblastoma and renal cell carcinoma cell lines. The elevated level of HIF2a protein was in certain tumor cell types accompanied by down-regulation of HIF1a protein levels, indicating that high Notch signaling may drive a HIF1a-to-HIF2a switch. At the transcriptome level, the presence of HIF2a was required for approximately 21% of all Notch-induced genes: among the 1062 genes that were upregulated by Notch in medulloblastoma cells during normoxia, upregulation was abrogated in 227 genes when HIF2a expression was knocked down by HIF2a siRNA. In conclusion, our data show that Notch signaling affects the hypoxic response via regulation of HIF2a, which may be important for future cancer therapies. Overall design: DAOY-NERT2 cells, +/- Notch induction by Tamoxifen (TMX) for 48 hours, +/- hypoxia (1% O2) treatment for 48 hours, where HIF1a or HIF2a had been knocked down by siRNA, were subjected to RNA sequencing. The quality of the cDNA libraries was tested on an Agilent 2100 bioanalyzer. The libraries were sequenced on an Illumina HiSeq 2000 system, and the reads were aligned to the human genome (assembly hg19) and a transcriptome database (RefSeq and Ensembl) using bowtie. RPKM values were generated using rpkmforgenes.
Publication Title
Notch signaling promotes a HIF2α-driven hypoxic response in multiple tumor cell types.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Human Exon 1.0 ST Array (huex10st)
Description
We compared the transcriptome at gene expression level in hypoxic and normoxic conditions.
Publication Title
Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples