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GSE136276
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- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER1 breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identi?ed differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissues response to an existing tumor.
Publication Title
Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile
Publication Title
Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 11 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Amputation of heart tissue followed by regeneration of the heart. Samples were taken at 0 hpa (hours post-amputation), 6 hpa, 12 hpa, 24 hpa, 3 dpa and 5 dpa.
Publication Title
Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration.
Sample Metadata Fields
Specimen part, Time
View Samples- Caenorhabditis elegans
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
C. elegans transcriptome component of "Genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum"
Publication Title
The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 52 Downloadable Samples
- Illumina HiSeq 2000
Description
We investigate the biological effects of radiation using Drosophila Melanogaster as a model organism, focusing on gene expression and lifespan analysis to determine the effect of different radiation doses. Our results support a threshold effect in response to radiation: no effect on lifespan and no permanent effect on gene expression is seen at doses below 10,000 Roentgens. Overall design: Adult male Drosophila were irradiated 2 days after eclosion, with one of 6 radiation doses: 10; 1,000; 5,000; 10,000; 20,000 Roentgens. Samples were taken at 3 time points (2, 10 and 20 days post-irradiation).
Publication Title
Drosophila melanogaster show a threshold effect in response to radiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 39 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Expression data from four different lifespan-extending conditions: dietary restriction in two different genetic backgrounds (canton-s and a yw, w1118 combination), sir2 overexpression and p53 knockdown (+/-).
Publication Title
Comparative transcriptional profiling identifies takeout as a gene that regulates life span.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm. Overall design: 4 conditions; 3 samples per condition. Young adults are 1d old adults without visible eggs. Aged adults are 6th day adults, post-egg-laying. The fog-2 mutant strain used was JK574
Publication Title
The <i>Caenorhabditis elegans</i> Female-Like State: Decoupling the Transcriptomic Effects of Aging and Sperm Status.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level.
Publication Title
Comparative transcriptional pathway bioinformatic analysis of dietary restriction, Sir2, p53 and resveratrol life span extension in Drosophila.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
A/J mice are genetically predisposed to spontaneous and/or chemically-induced lung tumors while C57BL/6J (B6) mice are resistant. This genetic disparity provides a unique scenario to identify molecular mechanisms associated with the lung response to welding fume at the transcriptome level.
Publication Title
Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.
Sample Metadata Fields
Treatment
View Samples