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Mus musculus
30 Downloadable Samples
Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Exposure to aristolochic acid (AA) is linked to kidney disease and urothelial cancer in humans. The major carcinogenic component of the AA plant extract is aristolochic acid I (AAI). The transcription factor p53 acts as a tumour suppressor and is frequently mutated in AA-induced tumours. Using a mouse model, we previously showed that Trp53 genotype impacts on AAI-induced nephrotoxicity in vivo (i.e. p53 protects from AAI-induced renal proximal tubular injury), but the underlying mechanism(s) involved remain to be further explored. In the present study, we investigated the impact of p53 on AAI-induced gene expression in vivo by treating Trp53(+/+), Trp53(+/-) and Trp53(-/-) mice with 3.5 mg/kg body weight (bw) AAI daily for 6 days. The Clariom™ S Assay microarray was used to elucidate gene expression profiles in mouse kidneys after AAI treatment in order to identify potential mechanisms by which AAI drives renal injury in Trp53(-/-) kidneys. Principle component analysis and hierarchical clustering in Qlucore Omics Explorer showed that gene expression in AAI-exposed Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys is treatment-dependent. However, gene expression profiles did not segregate in a clear-cut manner according to Trp53 genotype, hence further investigations were performed by pathway analysis with MetaCore™. Several pathways, such as those related to epithelial-to-mesenchymal transition, transcription of hypoxia-inducible factor 1 targets, renal injury and secretion of xenobiotics were significantly altered to varying degrees for AAI-exposed kidneys. The top ten up-regulated genes included cyclin-dependent kinase inhibitor 1a (Cdkn1a), a mediator of cell cycle arrest; and neutrophil gelatinase-associated lipocalin (Ngal), which has been shown to play a role in nephritis by promoting inflammation and apoptosis. Members of the solute carrier (Slc) family (i.e. Slc22a2, Slc22a6, Slc22a7, Slc22a8) were amongst the top ten down-regulated genes. Pathway analysis also identified genes that are uniquely affected by AAI treatment in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys. Apoptotic pathways were modulated in Trp53(+/+) kidneys; whereas oncogenic and pro-survival pathways were significantly altered for Trp53(+/-) and Trp53(-/-) kidneys, respectively. Microarray gene expression analysis identified significant toxicogenomic responses to AAI that give novel insights into its mechanism of nephrotoxicity. Alterations of biological processes by AAI in Trp53(+/+), Trp53(+/-) and Trp53(-/-) kidneys could explain the mechanisms by which p53 protects from or p53 loss drives AAI-induced renal injury in vivo.
Publication Title
The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Through genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
Publication Title
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Through genome-wide transcriptional comparisons, this study interrogates the capacity of iPSCs to accurately model pathogenic signatures of structural cardiac defects. Herein, we studied the molecular etiology of structural cardiac defects in Nos3-/- mice via transcriptional analysis of stage-matched embryonic and iPSC-derived tissues. In vitro comparisons of differentiated embryoid bodies were calibrated to in utero benchmarks of health and disease. Integrated systems biology analysis of WT and Nos3-/- transcriptional profiles revealed 50% concordant expression patterns between in utero embryonic and ex vivo iPSC-derived tissue. In particular, up-regulation of glucose metabolism (p-value = 3.95x10-12) and down-regulation of fatty acid metabolism (p-value = 6.71x10-12) highlight a bioenergetic signature of early Nos3 deficiency during cardiogenesis that can be recapitulated in iPSC-derived tissues. The in vitro concordance of early Nos3-/- disease signatures supports the utility of iPSCs as a cell-autonomous model of structural heart defects. Moreover, this study supports the use of iPSCs as a platform to pinpoint initial stages of cardiac pathogenesis.
Publication Title
Nos3-/- iPSCs model concordant signatures of in utero cardiac pathogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sample Metadata Fields
Sex, Specimen part
View Samples
GSE28083- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We are using genome-wide ChIP-seq with isoform-specific antibodies and chromatin from select tissues of mice challenged with different dietary conditions that enrich for specific SREBPs.
Publication Title
Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Arabidopsis plants growing under diurnal conditions were transferred to cold of approximately one day duration, starting at different times of the day. All comparisons are of unreplicated pairs and are thus not designed to identify cold-responsive gens in isolation but are rather to supplement existing publicly available data. The overall aim was to use a diverse set of experiments to see which factors have the greatest influence on the identity of cold-responsive genes.
Publication Title
Disruption of the Arabidopsis circadian clock is responsible for extensive variation in the cold-responsive transcriptome.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To address the neglected possibility for global mRNA changes in microarray experiments we developed a simple method to generate external controls for Affymetrix microarrays to allow these platforms to measure absolute mRNA expression at the global level. We used publicly available data to select probesets that never detect endogenous transcripts, and used PCR and IVT to generate synthetic mRNAs corresponding to them. After quality control and testing, these control transcripts were spiked into total RNA samples from plants before and after 24 h of cold treatment. Due to changes in the proportion of mRNA, these data reveal intensity-dependent bias in expression estimates based on standard all-gene normalizations. When not accounted for, this leads to false classification of the differential expression for thousands of genes.
Publication Title
Disruption of the Arabidopsis circadian clock is responsible for extensive variation in the cold-responsive transcriptome.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The whole blood was collected pre-treatment from rheumatoid arthritis patients starting the anti_TNF therapy. All patients were nave to anti_TNFs. The disease activity was measured using the DAS28 score at the pre-treatment visit1 (DAS28_v1) and 14 weeks after treatment visit3 (DAS28_v3). The response to the therapy was evaluated using the EULAR [European League Against Rheumatism] definition of the response. The objective of the data analysis was to identify gene expression coorelating with response as well as to identify genes that differentiate responders versus non-responders pre-treatment. The results of this investigation identified 8 trainscripts that predict responders vs. non-responders with 89% accuracy.
Publication Title
Convergent Random Forest predictor: methodology for predicting drug response from genome-scale data applied to anti-TNF response.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
We assessed the usability of microarrays, which base on formalin-fixed paraffin-embedded (FFPE) tissue.
Publication Title
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Sample Metadata Fields
Specimen part, Treatment
View Samples