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Rattus norvegicus
15 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD and PCB126 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg/day) (Toxic equivalence factor (TEF) = 1.0), PCB126 (30ng, 300ng or 1000ng/kg/day) (TEF = 0.1) or a vehicle control of corn oil:acetone (99:1) 5 days a week for 52 weeks.
Publication Title
Toxicogenomic analysis of exposure to TCDD, PCB126 and PCB153: identification of genomic biomarkers of exposure to AhR ligands.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 104 Downloadable Samples
Illumina HiSeq 2000
Description
Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction. Overall design: Endothelium from hypertensive mice were acutely extracted at two different ages (4 weeks and 22 weeks) and compared to endothelium from 22 week old normotensive mice.
Publication Title
Endothelial transcriptomics reveals activation of fibrosis-related pathways in hypertension.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of collecting duct response to low NaCl or high NaCl diet at the gene expression level. Results provide insight into transcriptional changes in principal and intercalated cells that occur in response to changes in dietary NaCl. Overall design: Total RNA obtained from collecting duct cells isolated from mice fed low NaCl or high NaCl diet for 5 days.
Publication Title
Salt-sensitive transcriptome of isolated kidney distal tubule cells.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain.
Publication Title
Cooperativity within and among Pten, p53, and Rb pathways induces high-grade astrocytoma in adult brain.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate Pten function in neonatal developing brain, we conditionally inactivated Pten in neural stem/progenitor cells at birth using a Nestin-CreER transgenic driver. Pten inactivation created a novel perivascular proliferative niche in the cerebellum that did not progress to malignancy during the lifespan of the mouse. Co-deletion of Pten and Trp53 synergized to cause fully penetrant medulloblastoma originating from a perivascular niche. The Pten and Trp53 double knock-out medulloblastomas showed an extensive and abnormal blood vessel network and advanced neuronal differentiation of tumor cells compared to medulloblastomas arising in Nestin-creER;Trp53fl/fl mice, suggesting that Pten loss promoted angiogenesis and neuronal differentiation in medulloblastoma. EdU pulse-chase experiments demonstrated a lineage hierarchy of the double knock-out medulloblastomas consistent with a perivascular cancer stem cell population. The Pten and Trp53 double knock-out medulloblastomas showed somatic loss of chromosomes 7, 13 and 16, and inactivating mutations in the tumor suppressor gene Ptch1. Gene expression profiles showed that this model recapitulated the subgroup of human medulloblastomas with de-regulated SHH signaling.
Publication Title
PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We are examining the genes that control initiation and progression of murine medulloblastomas that result from loss of patched. Approximately 25% of human medulloblastomas have mutations in patched or in other elements of the sonic hedgehog pathway. However, the cells from which these tumors originate (neural progenitors or stem cells), the cells that are responsible for tumor propagation (cancer stem cells), and the genes that are required for tumor progression are poorly understood. To address these questions, we have developed conditional patched knockout mice in which the gene is deleted in neural stem cells or progenitors. In addition, we have isolated a population of tumor-propagating cells from these tumors. By studying these models we will gain insight into the mechanisms of tumorigenesis and identify new targets for therapy.
Publication Title
Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE24156- Drosophila melanogaster
- 75 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We hypothesized that social interactions, such as those involved in courtship and mating, would lead to assayable changes in gene expression that may have important effects on individual reproductive success and fitness through alterations in physiology or changes in nervous system function.
Publication Title
Mating alters gene expression patterns in Drosophila melanogaster male heads.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples GSE24167- Drosophila melanogaster
- 75 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We hypothesized that social interactions, such as those involved in reproductive behaviors, would lead to immediate and assayable changes in gene expression that may have important effects on individual reproductive success and fitness through alterations in physiology or via short-term or long-term changes in nervous system function.
Publication Title
Socially-responsive gene expression in male Drosophila melanogaster is influenced by the sex of the interacting partner.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Malignant glioblastoma (GBM) is a highly aggressive brain tumor with a dismal prognosis and limited therapeutic options. Genomic profiling of GBM samples in the TCGA database has identified four molecular subtypes (Proneural, Neural, Classical and Mesenchymal), which may arise from different glioblastoma stem-like cell (GSC) populations. In the present study, we identify two GSC populations that produce GBM tumors by subcutaneous and intracranial injection with identical histological features. Gene expression analysis revealed that xenografts of GSCs grown as spheroid cultures had a Classical molecular subtype similar to that of bulk tumor cells. In contrast xenografts of GSCs grown as adherent cultures on laminin-coated plates expressed a Mesenchymal gene signature. Adherent GSC-derived xenografts had high STAT3 and ANGPTL4 expression as well as enrichment for stem cell markers, transcriptional networks and pro-angiogenic markers characteristic of the Mesenchymal subtype. Examination of clinical samples from GBM patients showed that STAT3 expression was directly correlated with ANGPTL4 expression, and that increased expression of these genes correlated with poor patient survival and performance. A pharmacological STAT3 inhibitor abrogated STAT3 binding to the ANGPTL4 promoter and exhibited anticancer activity in vivo. Taken together, we identified two distinct GSC populations that produce histologically identical tumors but with very different gene expression patterns, and a STAT3/ ANGPTL4 pathway in glioblastoma that may serve as a target for therapeutic intervention.
Publication Title
Molecular heterogeneity in a patient-derived glioblastoma xenoline is regulated by different cancer stem cell populations.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
Publication Title
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Sample Metadata Fields
Cell line
View Samples