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SRP029365
Homo sapiens
4 Downloadable Samples
Description
To identify genes regulated by BRD4 and to provide insight into new mechanisms de-regulated by BRD4, such as the response to oxidative stress, we integrated BRD4-binding regions with BRD4 gene expression data. For this analysis we performed BRD4 chromatin immunoprecipitation experiments and BRD4 knock down experiments followed by RNA-Seq analyses. By integration of both gene lists we identified top candidate genes regulated by BRD4. Overall design: HEK cells have been investigated for genomewide BRD4 binding sites and expression changes after knock down of BRD4. Illumina sequencing was used to gather data of the type ChIP Seq and mRNA Seq.
Publication Title
The bromodomain protein BRD4 regulates the KEAP1/NRF2-dependent oxidative stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Whole genome expression profiling of 40 healthy human twins (20 monozygotic, 20 dizygotic)
Publication Title
Genetic control of global gene expression levels in the intestinal mucosa: a human twin study.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
KRAS mutations occur in approximately 25% of non-small cell lung cancer (NSCLC). They account for the therapy resistance to EGFR inhibitors and are suggested to be difficult to target by specific drugs. Therefore, new therapies for KRAS mutant NSCLC are urgently needed. The histone H3K4 and H3K9 di/mono-demethylase KDM1A is a key epigenetic writer, aberrantly upregulated in many cancer types, including NSCLC. In order to understand the functional role of KDM1A in the progression of lung adenocarcinoma, KDM1A expression profiles were analysed in tissue microarrays (TMAs) including 182 lung adenocarcinoma. KDM1A expression correlated with high grade and metastasized tumor. To investigate the impact of KDM1A in lung adenocarcinoma development, we used the KRAS mutated A549 cell line to establish a shRNA-mediated stable KDM1A knockdown cell clone. Unexpectedly, KDM1A knockdown had only a slight effect on retardation of cell growth. However, cell invasion and self-renewal capability was significantly decreased by KDM1A inhibition. KDM1A knockdown in A549 cell resulted in a dramatic change in the transcriptome profile as determined by RNA-Seq. Interestingly, genes involved in the KRAS signature and lung epithelial marker genes were significantly affected upon KDM1A knockdown. Ingenuity pathway analysis also suggested that the alternative integrin ß3-KRAS signaling axis, which is involved in stem cell like properties, is abrogated upon KDM1A knockdown. Indeed, Integrin ß3 and its non-canonical ligand galectin-3 were strongly downregulated and their downstream NF-?B activity was decreased upon KDM1A knockdown. Finally, correlation of KDM1A to the Integrin ß3 level was validated in TMAs. Overall design: Determining the role of KDM1A in A549 cells, mRNA profiles of control and knockdown samples of A549 cells, generated by deep sequencing, in triplicate, using Illumina HiSeq 2500.
Publication Title
LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-B, e.g. TNFAIP3 (A20) and IER3.
Publication Title
Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.
Sample Metadata Fields
Cell line, Time
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The PUF family of RNA binding proteins has a conserved role in maintaining stem cell self-renewal. FBF is a C. elegans PUF that is required to maintain germline stem cells (GSCs). To understand how FBF controls GSCs, we sought to identify is target mRNAs. Briefly, we immunoprecipitated FBF-mRNA complexes from worm extracts and then used microarrays to identify the FBF-associated mRNAs. To focus on germline targets of FBF, we used a FBF-GFP transgene under the control of a germline promoter and we used an anti-GFP antibody to purify FBF-GFP from worm extracts. In parallel, we also processed a strain expressing TUBULIN-GFP in the germline to control for mRNAs that non-specifically co-purify with GFP. We found that FBF associates with >1,000 unique mRNAs and likely controls a broad network of key cellular and developmental regulators.
Publication Title
Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
Publication Title
The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
MiRNAs are discussed as diagnostic and therapeutic molecules. However, effective miRNA drug treatments with miRNAs are so far hampered by the complexity of the miRNA networks. To identify potential miRNA drugs in colorectal cancer, we profiled miRNA and mRNA expression in matching normal, tumor and metastasis tissues of eight patients by Illumina sequencing. We identified miRNA-1 as top candidate differentially expressed in tumor and metastasis. Furthermore, miRNA-1 was de-regulated in 16 additional tumor entities underscoring its central role in tumor pathogenesis. Functional analyses showed an additive effect of miRNA-1 with camptothecin treatment. We used a systems-biology simulation of cellular cancer models implemented in PyBios to investigate miRNA-1 function and assessed the effects of depletion as well as overexpression in terms of miRNA-1 as a potential treatment option. In this system miRNA-1 treatment reverted the disease phenotype with different effectiveness among the patients. Scoring the gene expression changes obtained through mRNA-Seq from the same patients we show that the combination of deep sequencing and systems biological modeling can help to identify patient-specific responses to miRNA treatments. We present this data as guideline for future pre-clinical assessments of new and personalized therapeutic options. Overall design: Examination of miRNA expression values by Illumina sequencing of matched benign, tumor and metastasis tissues of 8 colorectal cancer patients. For 4 of these patients all tissues have been resequenced to obtain mRNA expression values.
Publication Title
High-throughput miRNA and mRNA sequencing of paired colorectal normal, tumor and metastasis tissues and bioinformatic modeling of miRNA-1 therapeutic applications.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPAR/ mice to allow exploration of the specific contribution of PPAR. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPAR agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPAR-dependent manner, emphasizing the importance of PPAR in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPAR had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPAR.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus, Homo sapiens
- 46 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Publication Title
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples