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GSE73302
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
We compared the gene expression of A549 cells following 24 and 48 hours of treatment with a no-observed-effect level dose of cisplatin. The objective of the study is to identify genes that are differentially expressed in response to sub-lethal doses of cisplatin. This study helps identify not only treatment responses but also changes in gene expression that may confer cytoprotective mechanisms that allow these cells to survive treatment and to develop treatment resistance.
Publication Title
Combined Use of Gene Expression Modeling and siRNA Screening Identifies Genes and Pathways Which Enhance the Activity of Cisplatin When Added at No Effect Levels to Non-Small Cell Lung Cancer Cells In Vitro.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Chronic inflammation leading to pro-inflammatory macrophage infiltration contributes to the pathogenesis of type 2 diabetes and subsequently the development of diabetic nephropathy. Mesenchymal stem cells (MSCs) possess unique immunomodulatory and cytoprotective properties making them an ideal candidate for therapeutic intervention
Publication Title
Human mesenchymal stem cells alter the gene profile of monocytes from patients with Type 2 diabetes and end-stage renal disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Astrocytes from optic nerve head from donors with and without glaucoma
Publication Title
Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 122 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aldokatoreductases (AKRs) represent a gene superfamily that code for monomeric, soluble NAD(P)H-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that functions to eliminate retinals, has been observed to be upregulated in squamous metaplasma and non small cell lung cancer, and has been suggested as a diagnostic marker specific to tobacco-related carcinogenesis. In the context of the link of smoking and lung cancer and the enhanced expression of AKR1B10 expression in lung cancer, we hypothesize that enhanced expression of AKR1B10 may be initiated in healthy smokers, prior to the development of any evidence of lung cancer. For this purpose, expression of AKR1B10 was assessed at the mRNA level using microarrays in the large airway epithelium (21 healthy nonsmokers, 31 health smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fiberoptic bronchoscopy and brushing, as well as assessment in a subset of this population by TaqMan PCR and in endobronchial biopsies by Western analysis and immunohistochemistry. Compared to healthy nonsmokers, ARK1B10 mRNA levels were markedly upregulated in both the large and small airway epithelium of healthy smokers (large airway microarray p<0.0001, small airway p<0.0001; TaqMan large airway, p<0.02, small airway p<0.01). Consistent with the mRNA data, AKR1B10 protein was significantly upregulated in the airway epithelium of healthy smokers as assessed by Western analysis and by immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells of the normal epithelium. Finally, cigarette smoke extract mediated up-regulation of AKR1B10 in airway epithelial cells in vitro. Thus, smoking per se mediates up-regulation of AKR1B10 expression in the airway epithelium of healthy smokers with no evidence of lung cancer. In the context of these observations, and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced up-regulation of AKR1B10 may be an early process in the multiple events leading to the develop of lung cancer.
Publication Title
Smoking-induced upregulation of AKR1B10 expression in the airway epithelium of healthy individuals.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of human ADPGK, which encodes an ADP-dependent glucokinase (ADPGK), in tumour cell lines. The hypothesis tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two tumour cell lines (H460 and HCT116). All four lines had frameshift mutations in all alleles at the target site in exon 1 of ADPGK, and were ADPGK-null by immunoblotting. ADPGK knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 213% for the parental line to 6.40.8% (p=0.002) and 4.30.8% (p=0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when ADPGK was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of ADPGK in HCT116 cells caused few changes in global gene expression, knockout of ADPGK in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no effect on glycolysis as measured by glucose consumption or lactate formation under oxic or anoxic conditions, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the ADPGK knockouts, in some cases markedly so. Collectively, the results demonstrate that ADPGK can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of ADPGK is cell line dependent and appears to be unrelated to priming of glycolysis.
Publication Title
Expression and role in glycolysis of human ADP-dependent glucokinase.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 75 Downloadable Samples
Illumina HiSeq 2500
Description
In the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of the aorta-gonad-mesonephros region from E9.5 embryos and E10.5 embryos sub-dissected into dorsal (AoD), ventral (AoV) and urogenital ridges (UGR) and pooled from between 15 and 34 embryos in three separate experiments.
Publication Title
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 61 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To study the effect of structural changes on expression, we assessed gene expression in genomic disorder mouse models. Both a microdeletion and its reciprocal microduplication mapping to mouse chromosome 11 (MMU11), which model the rearrangements present in Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes patients, respectively, have been engineered. We profiled the transcriptome of five different tissues affected in human patients in mice with 1n (Deletion/+), 2n (+/+), 3n (Duplication/+) and uniallelic 2n (Deletion/Duplication) copies of the same region in an identical genetic background. The most differentially expressed transcripts between the four studied genotypes were ranked. A highly significant propensity, are mapping to the engineered SMS/PTLS interval in the different tissues. A statistically significant overrepresentation of the genes mapping to the flanks of the engineered interval was also found in the top-ranked differentially expressed genes. A phenomenon efficient across multiple cell lineages and that extends along the entire length of the chromosome, tens of megabases from the breakpoints. These long-range effects are unidirectional and uncoupled from the number of copies of the copy number variation (CNV) genes. Thus, our results suggest that the assortment of genes mapping to a chromosome is not random. They also indicate that a structural change at a given position of the human genome may cause the same perturbation in particular pathways regardless of gene dosage. An issue that should be considered in appreciating the contribution of this class of variation to phenotypic features.
Publication Title
Phenotypic consequences of copy number variation: insights from Smith-Magenis and Potocki-Lupski syndrome mouse models.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
In the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of OP9 cells grown in flat, submersed culture or reaggregate and cultured at the liquid-gas interface were compared.
Publication Title
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with preiods of active disease followed by remission.
Publication Title
Transcriptional analysis of the intestinal mucosa of patients with ulcerative colitis in remission reveals lasting epithelial cell alterations.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tolerogenic dendritic cells (tol-DCs) offer a promising therapeutic potential for autoimmune diseases. Tol-DCs have been reported to inhibit immunogenic responses, yet little is known about the mechanisms controlling their tolerogenic status, as well as associated specific markers. Here we show that the anti-inflammatory TAM receptor tyrosine kinase MERTK, is highly expressed on clinical grade dexamethasone-induced human tol-DCs and mediates their tolerogenic effect. Neutralization of MERTK in allogenic mixed lymphocyte reactions as well as autologous DC-T cell cultures leads to increased T cell proliferation and IFN-g production. Additionally, we identify a previously unrecognized non-cell autonomous regulatory function of MERTK expressed on DCs. Recombinant Mer-Fc protein, used to mimic MERTK on DCs, suppresses nave and antigen-specific memory T cell activation. This mechanism is mediated by the neutralization of the MERTK agonist Protein S (PROS1) expressed by T cells. We find that MERTK and PROS1 are expressed in human T cells upon TCR activation and drive an autocrine pro-proliferative mechanism. Collectively, these results suggest that MERTK on tol-DCs directly inhibits T cell activation through the competition for PROS1 interaction with MERTK in the T cells. Targeting MERTK may provide an interesting approach to effectively increase or suppress tolerance for the purpose of immunotherapy.
Publication Title
MERTK as negative regulator of human T cell activation.
Sample Metadata Fields
No sample metadata fields
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