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GSE85957
Rattus norvegicus
57 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We investigated an acute kidney injury (AKI) model in rats induced by cisplatin (Cp) administration. The cisplatin is widely used since its biochemical and histopathological characteristics are representative of drug-induced AKI in humans. Male Wistar rats were dosed once ip with 0, 1 and 3 mg/kg cisplatin. Tubular necorsis was observed histopathologically in all treated rats and war recovery on day 26. Gene expression profiling of the kidney cortex with microarrays 3, 5, 8, and 26 days after single administration of 3mg/kg Cp revealed a major profile pattern characterized by maximally increased and decreased mRNA levels on day 8, with clear changes already found 3 days after treatment for about half of the mRNAs. The mRNA expression pattern after administration of 1mg/kg Cp was overall similar, yet with a dose-dependent smaller fold-change. In summary we found 274 mRNAs showing significantly altered levels in the kidney of which 162 were increased and 112 decreased, respectively. Functional interpretation of the proteins encoded by these mRNAs revealed induction of a DNA damage response likely caused by the known molecular activity of Cp as DNA alkylating agent. Increased mRNAs associated with apoptosis (encoded by the corresponding genes like B-cell lymphoma 3-encoded protein, Bcl3; mouse double minute 2 homolog, Mdm2; p21/WAF1 also known as cyclin-dependent kinase inhibitor 1), cell cycle regulation (encoded by the corresponding genes like Cyclin-G1, Ccng1; B-cell translocation gene 2, Btg2) and stress response may have partly been induced by the DNA damage, but also by the kidney damage associated with Cp administration. Increased levels of mRNAs indicating regeneration (encoded by the corresponding genes like SPARC- related modular calcium-binding protein 2, Smoc2; Tenascin C, Tnc) and decreased levels of mRNAs coding for proteins related to kidney function, indicating dedifferentiation, are likely related to the observed kidney injury.
Publication Title
Comparison of the MesoScale Discovery and Luminex multiplex platforms for measurement of urinary biomarkers in a cisplatin rat kidney injury model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans. Male Wistar Kyoto (WKY) and Sprague Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days.
Publication Title
Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in Rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 57 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We investigated a drug-induced liver injury (DILI) model in rats induced by methapyrilene (MPy) administration. MPy, a former antihistamine and anticholinergic drug, was withdrawn in the 1970ties due to its ability to initiate hepatocarcinogenesis and is now used to induce hepatobiliary injury and biliary epithelial cell hyperplasia. Male Wistar rats (810 weeks old, weighing 170200 g) were randomly assigned to three dosing groups (n=6 per group and time-point) and dosed with MPy at 0, 30 and 80 mg/kg/day by oral gavage. After 4, 8 or 15 days, or after 14 days followed by a recovery period of 10 days (day 24) rats were sacrificed. Increased levels of ALAT, ASAT, AP and -GT as well as bili-t and total bile acids indicated liver damage (AP and GT indicating biliary effects). They were detectable on day 7 at the high dose of 80 mg/kg MPy and persisted until day 15 at end of treatment. Histopathologically, vacuolation and necrosis of the hepatocytes (predominantly in the periportal region) were seen starting on day 3 - especially in animals treated with 80 mg/kg MPy. These findings were accompanied by periportal mononuclear inflammatory cell filtration. Bile duct proliferation, bile duct hyperplasia and increased numbers of mitoses of hepatocytes were evident at all treatment time points. The frequency and severity of these findings increased with dose and duration of the treatment. Gene expression analysis in liver tissues revealed highly significant transcriptional changes in the high dose group, detectable on day 4 and intensifying over time. Besides genes associated with apoptosis (CASP4, CASP12), detoxification (CYB4B) and proliferation (p21, CCNG1) several were related to bile acid metabolism or transport. For example, bile acid exporters OATP1, NTCP, OATP4 and MOAT1/ OATPB as well as the putative bile acid metabolizing enzymes AMACR, BAAT and ACOX2 were found down regulated in response to MPy treatment. In contrast, mRNAs encoding putative bile acid importers MRP2 and ABCC4 / MRP4 were found up regulated. Most of the deregulated levels returned to control values during the recovery phase except OATP1, MOAT1/ OATPB, which remained slightly elevated. Interestingly, OATP4 followed an inverse trend of deregulation after 10 days of recovery, presumably due to overcompensation. Overall, the expression changes found associated with bile acid metabolism or transport could be linked to detected bile acid level alterations in liver and plasma.
Publication Title
Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Tissues of Arabidopsis plants overexpressing artificial microRNAs were compared to wild_type and respective target gene mutants (duplicate arrays)
Publication Title
Highly specific gene silencing by artificial microRNAs in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Publication Title
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 415 Downloadable Samples
Illumina HiSeq 2500
Description
SMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Danio rerio
- 28 Downloadable Samples
- NextSeq 500
Description
Wild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2500
Description
Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Publication Title
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptomic changes induced in the human liver cell line HepG2 by 7M of cisplatin after treatment for 12, 24 and 48h
Publication Title
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples