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SRP103770
Mus musculus
16 Downloadable Samples
Illumina HiSeq 2500
Description
G9a mediates a transcriptional switch, and activates the Notch pathway to coordinate endothelial cell and trophoblast proliferation to promote vascular maturation in the placenta. Overall design: Examination of global transcriptional profiles in control and mutant placenta labyrinth at 2 developmental stages (E12.5 and 13.5).
Publication Title
G9a controls placental vascular maturation by activating the Notch Pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The expression of a very large number of genes changes as male germ cells pass through differentiation into spermatids and then sperm. Much of this transcriptional programme requires the activity of the meiotic arrest genes.
Publication Title
The RNA export factor, Nxt1, is required for tissue specific transcriptional regulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 3000
Description
Dysfunctions in mitochondria dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). Recently, it was shown that an inherited form of PD and dementia is caused by new mutations in the OPA1 gene, which encodes for a key player of mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1 mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectively rescued this survival deficit. Additionally, dampening necroptosis in MPTP treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both the early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a promising therapeutic target for PD. Overall design: 3 replicates for control and 3 replicates for OPA1 F38D mutant cells
Publication Title
Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson's Disease Models.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups.
Publication Title
Tumor immunobiological differences in prostate cancer between African-American and European-American men.
Sample Metadata Fields
Race
View Samples- Homo sapiens
- 160 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Affordable early screening in subjects with high risk of lung cancer has great potential to improve survival from this deadly disease. We measured gene expression from lung tissue and peripheral whole blood (PWB) from adenocarcinoma cases and controls to identify dysregulated lung cancer genes that could be tested in blood to improve identification of at-risk patients in the future. Genome-wide mRNA expression analysis was conducted in 153 subjects (73 adenocarcinoma cases, 80 controls) from the Environment And Genetics in Lung cancer Etiology (EAGLE) study using PWB and paired snap-frozen tumor and non-involved lung tissue samples. Analyses were conducted using unpaired t-tests, linear mixed effects and ANOVA models. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the identified biomarkers. We identified 50 dysregulated genes in stage I adenocarcinoma versus control PWB samples (False Discovery Rate 0.1, fold change 1.5 or 0.66). Among them, eight (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3) differentiated paired tumor versus non-involved lung tissue samples in stage I cases, suggesting a similar pattern of lung cancer-related changes in PWB and lung tissue. These results were confirmed in two independent gene expression analyses in a blood-based case-control study (n=212) and a tumor-non tumor paired tissue study (n=54). The eight genes discriminated patients with lung cancer from healthy controls with high accuracy (AUC=0.81, 95% CI=0.74-0.87). Our finding suggests the use of gene expression from PWB for the identification of early detection markers of lung cancer in the future.
Publication Title
A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
- IlluminaHiSeq2000
Description
Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P?<?1.0?×?10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers'' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P?=?1.13?×?10-62) and CYP1B1 (P?<?2.49?×?10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis. Overall design: RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.
Publication Title
Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 107 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Tobacco smoking is responsible for over 90% of lung cancer cases, and yet the precise molecular alterations induced by smoking in lung that develop into cancer and impact survival have remained obscure. We performed gene expression analysis using HG-U133A Affymetrix chips on 135 fresh frozen tissue samples of adenocarcinoma and paired noninvolved lung tissue from current, former and never smokers, with biochemically validated smoking information. ANOVA analysis adjusted for potential confounders, multiple testing procedure, Gene Set Enrichment Analysis, and GO-functional classification were conducted for gene selection. Results were confirmed in independent adenocarcinoma and non-tumor tissues from two studies. We identified a gene expression signature characteristic of smoking that includes cell cycle genes, particularly those involved in the mitotic spindle formation (e.g., NEK2, TTK, PRC1). Expression of these genes strongly differentiated both smokers from non-smokers in lung tumors and early stage tumor tissue from non-tumor tissue (p<0.001 and fold-change>1.5, for each comparison), consistent with an important role for this pathway in lung carcinogenesis induced by smoking. These changes persisted many years after smoking cessation. NEK2 (p<0.001) and TTK (p=0.002) expression in the noninvolved lung tissue was also associated with a 3-fold increased risk of mortality from lung adenocarcinoma in smokers. Our work provides insight into the smoking-related mechanisms of lung neoplasia, and shows that the very mitotic genes known to be involved in cancer development are induced by smoking and affect survival. These genes are candidate targets for chemoprevention and treatment of lung cancer in smokers.
Publication Title
Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Inflammatory mediators play a role in the pathogenesis/progression of chronic heart failure (CHF). The aim of the present study was to identify diagnostic/prognostic markers and gene expression profiles of CHF vs control.
Publication Title
Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The ability of dying cells to activate antigen presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here we show that engulfed cells only containing cytosolic dsDNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs, via extrinsic STING-signaling.
Publication Title
Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells.
Sample Metadata Fields
Specimen part
View Samples