Filters
Technology
Platform
GSE49817
Homo sapiens
18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study determined the genes that are differetially expressed when regulatory T cells were stimulated in vitro with IL-2
Publication Title
Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Objective: identify novel and relevant aspects of Sorafenib action on liver cancer cells. We found that in rat hepatocholangiocarcinoma (LCSC-2) cells, exposure to the MEK/multikinase inhibitor sorafenib did not inhibit ERK phosphorylation nor induced appreciable cell death in the low micromolar range; instead, the drug elicited a raise of intracellular reactive oxygen species (ROS) accompanied by a severe decrease of oxygen consumption and intracellular ATP levels, all changes consistent with mitochondrial damage. Moreover, Sorafenib induced depolarization of isolated rat liver mitochondria, indicating a possible direct effect on the organelle. Microarray analysis of gene expression in sorafenib-trated cells revealed a metabolic reprogramming toward aerobic glycolysis, that likely accounts for resitance to drug toxicity in this cell line. Importantly, cytotoxicity was strongly potentiated by glucose withdrawal from the culture medium or by the glycolytic inhibitor 2-deoxy-glucose, a finding also confirmed in the highly malignant melanoma cell line B16F10. Mechanistic studies revealed that ROS are pivotal to cell killing by the Sorafenib + 2DG combination, and that a low content of intracellular oxidants is associated with resistance to the drug; instead, Thr172phosphorylation/activation of the AMP-activated protein kinase (AMPK), induced by Sorafenib, may exert protective effects, since cytotoxicity was enhanced by an AMPK specific inhibitor and prevented by the AMPK activator Metformin. Overall, this study identifies novel and relevant aspects of Sorafenib action on liver cancer cells, including mitochondrial damage, induction of ROS and a metabolic cell reprogramming towards glucose addiction, potentially exploitable in therapy.
Publication Title
The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 32 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
Successfully fighting infection requires a properly tuned immune system. Recent epidemiological studies link exposure to pollutants that bind the aryl hydrocarbon receptor (AHR) during development with poorer immune responses later in life. Yet, how developmental triggering of AHR durably alters immune cell function remains unknown. Using a mouse model, we show that developmental activation of AHR leads to long-lasting reduction in the response of CD8+ T cells during influenza virus infection, cells critical for resolving primary infection. Combining genome-wide approaches, we demonstrate that developmental activation alters DNA methylation and gene expression patterns in isolated CD8+ T cells prior to and during infection. Altered transcriptional profiles in CD8+ T cells from developmentally exposed mice reflect changes in pathways involved in proliferation and immunoregulation, with an overall pattern that bears hallmarks of T cell exhaustion. Developmental exposure also changed DNA methylation across the genome, but differences were most pronounced following infection, where we observed inverse correlation between promoter methylation and gene expression. This points to altered regulation of DNA methylation as one mechanism by which AHR causes durable changes in T cell function. Discovering that distinct gene sets and pathways were differentially changed in developmentally exposed mice prior to and after infection further reveals that the process of CD8+ T cell activation is rendered fundamentally different by early life AHR signaling. These findings reveal a novel role for AHR in the developing immune system: regulating DNA methylation and gene expression as immune cells respond to viral infection later in life. Overall design: In this study, two biological replicates were collected for each of four treatment groups: developmental exposure to vehicle control (Veh) and naïve, developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and naïve, developmental exposure to Veh and infected, developmental exposure to TCDD and infected. For each sample, both RNA-seq and methylated DNA immunoprecipitation (MeDIP)-seq were performed.
Publication Title
Linking the aryl hydrocarbon receptor with altered DNA methylation patterns and developmentally induced aberrant antiviral CD8+ T cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
The ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, and subject to disruption by exposure to environmental agents such as hexavalent chromium. Cr(VI) exposure can cause chromosomal disruption through formation of Cr-DNA adducts, free radical-induced DNA damage, and DNA-Cr-protein and DNA-Cr-DNA cross-links, all of which may disrupt chromatin remodeling mechanisms responsible for maintenance or controlled modification of epigenetic homeostasis. In addition, dose-response analyses have shown that acute exposures to high-concentrations of Cr(VI) and chronic exposures to low-concentrations of the same agent lead to significantly different transcriptomic and genomic stability outcomes. To investigate how transcriptional responses to chromium exposure might correlate to structural changes in chromatin, we have used whole genome Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis coupled with deep sequencing to identify regions of the genome that switch from open to closed chromatin or vice versa in response to exposure to varying Cr(VI) concentrations. We find that the switch affects gene expression levels in the target areas that vary depending on Cr(VI) concentration. At either Cr(VI) concentration, chromatin domains surrounding binding sites for AP-1 transcription factors become significantly open, treatment whereas BACH2 and CTCF binding sites are open solely at the low and high concentrations, respectively. Our results suggest that FAIRE may be a useful technique to map chromatin elements targeted by DNA damaging agents for which there is no prior knowledge of their specificity, and to identify subsequent transcriptomic changes induced by those agents. Overall design: Cr25 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq. Cr0.5 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq.
Publication Title
Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 1000
Description
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene-environment interactions. In addition, many AHR target genes that have been identified by genome-wide profiling have morphogenetic functions, suggesting that AHR activation may play a role in embryonic development. To address this hypothesis, we studied the consequences of AHR activation by TCDD, its prototypical ligand, during spontaneous mouse ES cell differentiation into contractile cardiomyocytes. Treatment with TCDD or shRNA-mediated AHR knockdown significantly decreased the ability of cardiomyocytes to contract and the expression of cardiac markers in these cells. An AHR-positive embryonic stem cell lineage was generated that expressed puromycin resistance and eGFP under the control of the AHR-responsive Cyp1a1 promoter. Cells of this lineage were over 90% pure and expressed AHR as well as cardiomyocyte markers. Analysis of temporal trajectories of global gene expression in these cells shows that activation of the AHR/TCDD axis disrupts the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and Trithorax Group genes. More than 50% of the homeobox factors so regulated do not have AhRE sites in their promoters, indicating that AHR activation may establish a complex regulatory network that reaches beyond direct AHR signaling and is capable of disrupting various aspects of embryonic development, including cardiomyocyte differentiation. Overall design: mRNA profiles of WT and selected AHR positive cells at different differentiation days treated with and without TCDD in duplicates
Publication Title
Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis.
Sample Metadata Fields
Treatment, Subject
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study was designed to provide additional insight into testicular hormone production and responsiveness in the orl strain and complement ongoing efforts to characterize the genetic basis of cryptorchidism in this isolated rat colony.
Publication Title
Cryptorchidism in the orl rat is associated with muscle patterning defects in the fetal gubernaculum and altered hormonal signaling.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) wild type plants under phosphate starvation stress and in plants with altered PHR1(-like) activity, comparing mutants of phr1 and phr1-phl1 grown in phosphate-lacking medium. Results show the central role of PHR1 and functionally redundant members of its family in the control of transcriptional responses to Pi starvation.
Publication Title
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We performed a transcriptomic analysis of Pi starvation responses in Arabidopsis thaliana (Columbia-0) phr1 mutant plants expressing PHR1 in presence of cicloheximide, that inhibit protein translation, thus preventing any effect of PHR1 on the expression of indirect targets. Results show the primary target genes of PHR1 in the responses to Pi starvation.
Publication Title
A central regulatory system largely controls transcriptional activation and repression responses to phosphate starvation in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
In order to identify NR2E3-specific gene expression pattern in liver cancer cell line, small hairpin RNA for NR2E3 was transfected in HepG2 human liver cancer cells. Overall design: Two groups of samples are included: 1. sh control (shCT_1, shCT_2); 2. shNR2E3 (shNR2E3 KO_1 , shNR2E3 KO_2). Gene expression profiles of NR2E3 depleted cells were compared to that of shRNA controls. Experiments were performed in HepG2 cells.
Publication Title
Loss of NR2E3 represses AHR by LSD1 reprogramming, is associated with poor prognosis in liver cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Cancer-associated skeletal muscle fatigue is a common problem in clinical oncology that is often associated with cancer cachexia, but is not exclusively observed in cachectic patients. The majority of breast cancer (BC) patients report muscle fatigue despite cachexia being relatively rare in this patient population. The clinically relevant phenotype of muscle fatigue in the absence of frank cachexia has no established model system and no approved therapeutic agents. Here, we utilize a breast cancer patient-derived orthotopic xenograft (BC-PDOX) model to recapitulate the human phenotype of tumor-induced muscle fatigue without muscle wasting, and utilized RNA-sequencing to identify pathways contributing to this clinically common phenomenon.
Publication Title
Human Breast Cancer Xenograft Model Implicates Peroxisome Proliferator-activated Receptor Signaling as Driver of Cancer-induced Muscle Fatigue.
Sample Metadata Fields
Sex, Specimen part
View Samples