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GSE29868
Homo sapiens
50 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Statins are widely used cholesterol-lowering drugs that inhibit HMG-CoA reductase, a key enzyme in cholesterol synthesis. In some cases, however, these drugs may cause a number of toxic side effects in hepatocytes and skeletal muscle tissue. Currently, the specific molecular mechanisms that cause these adverse effects are not sufficiently understood. In this work, genome-wide RNA expression changes in primary human hepatocytes of six individuals were measured at five time points upon atorvastatin treatment. A novel systems-level analysis workflow was applied to reconstruct regulatory mechanisms based on these drug-response data and available knowledge about transcription factor binding specificities, protein-protein interactions and protein-drug interactions. Several previously unknown transcription factors, regulatory cofactors and signaling molecules were found to be involved in atorvastatin-responsive gene expression. Some novel relationships, e.g., the regulatory influence of nuclear receptor NR2C2 on CYP3A4, were successfully validated in wet-lab experiments.
Publication Title
Inferring statin-induced gene regulatory relationships in primary human hepatocytes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Parkinsons disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression, or the A53T mutation, of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. Here, we used two mouse lines overexpressing human A53T-SNCA around ages 6 and 18 months and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. High pressure liquid chromatography analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also observed in SNCA deficient mice. In the striatum of aged A53TSNCA overexpressing mice, where DA levels were elevated, a paradoxical upregulation of dopamine receptors DRD1A and DRD2 was detected by immunoblots and autoradiography, findings compatible with the notion of abnormal vesicle release. Extensive transcriptome studies via microarrays and quantitative real-time RT-PCR validation of altered Homer1, Cb1, Atf2 and Pde7b transcript levels indicated a progressive reduction in the postsynaptic DA response. As functional consequences, long term depression was absent in corticostriatal slices from aged transgenic mice and an insidious decrease of spontaneous locomotor activity of these animals was found in open field tests. Taken together, the dysfunctional neurotransmission and decreased synaptic plasticity seen in the A53T-SNCA overexpressing mice reflects early functional changes within the basal ganglia resulting from synucleinopathy prior to frank neurodegeneration. Thus, preclinical stages of PD may be modeled in this mouse. Parkinsons disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression, or the A53T mutation, of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. Here, we used two mouse lines overexpressing human A53T-SNCA around ages 6 and 18 months and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. High pressure liquid chromatography analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also observed in SNCA deficient mice. In the striatum of aged A53TSNCA overexpressing mice, where DA levels were elevated, a paradoxical upregulation of dopamine receptors DRD1A and DRD2 was detected by immunoblots and autoradiography, findings compatible with the notion of abnormal vesicle release. Extensive transcriptome studies via microarrays and quantitative real-time RT-PCR validation of altered Homer1, Cb1, Atf2 and Pde7b transcript levels indicated a progressive reduction in the postsynaptic DA response. As functional consequences, long term depression was absent in corticostriatal slices from aged transgenic mice and an insidious decrease of spontaneous locomotor activity of these animals was found in open field tests. Taken together, the dysfunctional neurotransmission and decreased synaptic plasticity seen in the A53T-SNCA overexpressing mice reflects early functional changes within the basal ganglia resulting from synucleinopathy prior to frank neurodegeneration. Thus, preclinical stages of PD may be modeled in this mouse.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to identify an expression signature that might characterize the impact of Plasmodium parasites on NK cells, we have used Affymetrix oligonucleotide microarrays to examin the global gene expression profile of primary NK cells that have been co-incubated with P. falciparum infected red blood cells and have compared it to the expression pattern of NK genes induced by cytokine treatment.
Publication Title
No associated publication
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein. The mutant protein forms intracellular aggregates in the brain. However, the cellular mechanisms causing toxicity are still poorly understood and there are currently no effective treatments. In this study we show that administration of a rapamycin ester, CCI-779, improves motor performance in a transgenic mouse model of SCA3. CCI-779 inhibits mammalian target of rapamycin (mTOR) and hence upregulates protein degradation by autophagy. CCI-779 reduces the number of aggregates seen in the brains of transgenic mice and decreases levels of cytosolic soluble mutant ataxin-3, while endogenous wild-type protein levels remain unaffected. CCI-779 is designed for long-term use in patients and therefore represents a possible therapeutic strategy for the treatment of SCA3. Using this disease model and treatment paradigm we employed a microarray approach to investigate transcriptional changes that might be important in the pathogenesis of SCA3. This approach identified Usp15, which showed expression changes at both the mRNA and protein level. Usp15 levels were also changed in mice expressing another mutant polyglutamine protein, huntingtin. In total we identified 16 transcripts that were decreased in transgenic ataxin-3 mice that were normalised following CCI-779 treatment, as the number of transcripts changed was low and the magnitude of these changes was small we suggest that transcriptional dysregulation may not be an important step in the primary pathogenesis of SCA3.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and derive embryonic stem cell properties.
Publication Title
Generation of pluripotent stem cells from adult human testis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HIF-1 is an important transcription factor for immune responses to bacterial infection. We wanted to analyze the HIF-1 dependent gene expression upon S. aureus infection and analyzed the gene expression of HepG2 nt and HepG2 HIF-1-/- cells four hours upon infection using affymetrix human gene 1.0 st. gene arrays.
Publication Title
Hypoxia-inducible factor 1-regulated lysyl oxidase is involved in Staphylococcus aureus abscess formation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cultured immortalized cell lines have been extensively used to study the characteristics of various malignant stem cell clones and to optimize new treatment strategies. Nonetheless, the usefulness of such in vitro systems to recapitulate primary disease proved to be limited. Therefore, the design of more meaningful pre-clinical in vivo models ideally utilizing primary patient-derived material is of critical importance. In this context, the recently described NOD.Cg-Prkdcscid IL2rgtmWjl/Sz (NSG) mouse strain has been reported to sustain superior engraftment rates of patient-derived acute lymphatic and myeloid leukemic samples. However, limited data exist whether NSG-derived blasts retain their leukemogenecity over successive mouse generations and whether characteristics of this mouse model will indeed allow correlation to clinical parameters. In the present study, we thus engrafted NSG mice with 18 different pediatric B cell precursor ALL, AML and T-ALL samples and could demonstrate that NSG-derived blasts retained their leukemogenic profile with respect to immune-phenotype, chromosomal aberrations, transcriptome, flowcytometric- and PCR-minimal residual disease (MRD) marker expression. Moreover, the extent of leukemic engraftment and the overall survival of NSG mice highly correlated with the individual prognosis of pediatric B cell precursor ALL, AML and T-ALL patients. Thus, we here report on a complex in vivo model that provides a valuable tool for studying the heterogeneity of leukemic disease and for improving patient-tailored leukemia-targeting strategies .
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Analysis of gene expression data to evaluate candidate targets for immunotherapy.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Surrogate models have so far been missing that might allow the evaluation of graft-versus-leukemia effects in an individualized donor-patient-specific context. We here describe the generation of a NOD/SCID/IL2Rnull (NSG) leukemia mouse model that ideally resembles the biology of miscellaneous patient-specific leukemias. Following transfer of patient-derived blasts into NSG mice, various forms of pediatric haematological malignancies readily engrafted NSG recipients and NSG-derived leukemic cells indeed resembled the individual leukemia with respect to phenotype, chromosomal aberrations, transcriptome and MRD marker expression.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Effect of heat stress on wildtype COL-0 Arabidopsis and hsf4-7 double knock out plants.
Publication Title
Heat Shock Factors HsfB1 and HsfB2b Are Involved in the Regulation of Pdf1.2 Expression and Pathogen Resistance in Arabidopsis
Sample Metadata Fields
Age, Specimen part, Subject
View Samples