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SRP170634
Caenorhabditis elegans
15 Downloadable Samples
Illumina HiSeq 4000
Description
Inhibition of insulin/IGF-1 signaling (IIS) represents a promising avenue for the treatment of mitochondrial diseases, although many of the molecular mechanisms underlying this beneficial effect remain elusive. Here, we analyze the transcriptome of a well established model for mitochondrial deficiency, gas-1(fc21) mutant nematodes, which when placed in a genetic context of IIS inhibition, undergo metabolic rewiring leading to a massive lifespan extension Overall design: 5 biological replicates each of wild-type, gas-1(fc21) and age-1(hx546);gas-1(fc21) mutant nematodes (L4 stage) were analyzed by RNA Next Generation Sequencing
Publication Title
Multi-omics identify xanthine as a pro-survival metabolite for nematodes with mitochondrial dysfunction.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Most hepatocellular carcinomas in younger patients from Peru arise from non-cirrhotic livers. Histological examination of the non-tumor liver tissues highlights the presence of clear cell foci in a significant fraction of Peruvian patients with hepatocellular carcinoma.
Publication Title
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America.
Sample Metadata Fields
Specimen part, Disease stage, Subject
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- Mus musculus
- 147 Downloadable Samples
- Illumina HiSeq 2000
Description
The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the ß-blocker atenolol (ATE) and the ß-agonist isoproterenol (ISO). Differential expression analyses revealed a large set of genes responding to ISO (n=1770 at FDR=0.0001) and a comparatively small one responding to ATE (n=23 at FDR=0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r= -0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibited coherent transcription profiles across some strains and/or treatments. Correlations between such modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Our study provides new insights into the transcriptional response of the heart to perturbations of the ß-adrenergic system, implicating several new genes that had not been associated to this system previously. Overall design: Cardiac mRNA expression profiles of the various inbred mouse strains were examined either under baseline condition (control) or in response to chronic administration of isoproterenol or atenolol at 10 mg/kg per day for 2 weeks. Expression data were produced by RNA-sequencing, in triplicates, using the HiSeq 2000 Illumina platform. Only males, aged ten to twelve weeks on average, were included in the experimental protocol. Mouse ID numbers refer to those described in Berthonneche C. et al. PLoS One. 2009 Aug 12;4(8):e6610 (doi: 10.1371/journal.pone.0006610. PMID: 19672458). Corresponding individual phenotypic values, in particular heart rate, systolic blood pressure, electrocardiogaphic measurements and heart weight are available in dataset "maurer1" of the Mouse Phenome Database (http://phenome.jax.org/). Preparation of the sequencing libraries, RNA-sequencing and RNA expression quantitations were performed by the BGI.
Publication Title
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
We used Au nanoparticles (Au-NPs) as a model for studying particle specific effects of manufactured nanomaterials (MNMs) by examining the toxicogenomic responses in a model soil organism, free living nematode Caenorhabditis elegans. Global genome expression for nematodes exposed to 4-nm citrate-coated Au-NPs at the LC10 (5.9 mg L-1) revealed significant differential expression of 797 genes. The levels of expression for five genes (apl-1, dyn-1, act-5, abu-11, and hsp-4) were confirmed independently with qRT-PCR. Seven common biological pathways associated with 38 of these genes were identified. Activation of 26 pqn/abu genes from noncanonical Unfolded Protein Response (UPR) pathway and up-regulation of molecular chaperones (hsp-16.1, hsp-70, hsp-3 and hsp-4) were observed and are likely indicative of endoplasmic reticulum stress. Inhibition of abu-11 with RNAi showed increase in mortality in Au-NP exposed nematodes suggesting possible involvement of abu-11 (a gene associated with specific to C. elegans UPR) in a protective mechanism against Au-NPs. Exposure to Au-NPs also caused activation of genes involved in apoptosis and necrosis and resulted ultimately in 10% mortality. These results demonstrate that Au-NPs are bioavailable and cause adverse effects to a model ecoreceptor which activate both general and specific biological pathways.
Publication Title
Toxicogenomic responses of the model organism Caenorhabditis elegans to gold nanoparticles.
Sample Metadata Fields
Treatment
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
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
DNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic disease, diabetes, infertility and cancer. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 253 differentially modulated probe sets, identifying 217 well-characterized genes. A large part of these were associated with cell adhesion and/or angiogenesis and with transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway, were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems.
Publication Title
Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
The epicardium, an epithelium covering the heart, is essential for cardiac development. During embryogenesis, the epicardium provides instructive signals for the growth and maturation of cardiomyocytes and for coronary angiogenesis. We generated an in vitro model of human embryonic epicardium derived from human pluripotent stem cells (hPSC-epi). These cells were able to differentiate into cardiac fibroblasts (cf) and smooth muscle cells (smc) in vitro (hPSC-epi-cf and hPSC-epi-smc respectively). Furthermore, we showed that they improved maturation of hPSC-derived cardiomyocytes (hPSC-cardio) in vitro while neural crest cells derived from hPSC (hPSC-NC) could not. Furthermore, they improved survival of hPSC-cardio and stimulated angiogenesis when injected in a rat model of myocardium infarction. We performed mRNA sequencing of the hPSC-epi, hPSC-epi-cf, hPSC-smc and hPSC-NC in order to identify the secreted molecules specifically produced by the hPSC-epi and/or its derivatives in comparison with the hPSC-NC. Vascular smooth muscle cells have different embryonic origins and different properties depending on their location in the body. The coronary smooth muscle cells come from the epicardium while the aortic ones come from the mesoderm or the neural crest. We performed mRNA sequencing of human coronary artery smc and human aortic smc to identify a specific signature of the coronary smc. We also compared the genes expressed in the hPSC-epi-smc and the smc derived from hPSC-derived lateral plate mesoderm. Overall design: For hPSC-derived samples the three replicates are coming from three different in vitro differentiations from H9. For the human primary cells, the triplicates are technical replicates (three different wells from the same culture at the same passage)
Publication Title
Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.
Sample Metadata Fields
Specimen part, Subject
View Samples