This SuperSeries is composed of the SubSeries listed below.
Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations.
Specimen part
View SamplesPatient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease in disease relevant cells, as well as a promising source for cell replacement therapies for degenerative diseases. However one of the crucial limitations before realizing the full promise of this disease in a dish approach has been the inability to do controlled experiments under genetically defined conditions. This is particularly relevant for disorders with long latency periods, such as Parkinsons disease (PD), where in vitro phenotypes of patient-derived iPSCs are predicted to be subtle and susceptible to significant epistatic effects of genetic background variations. By combining zinc-finger nuclease (ZFN)-mediated genome editing and iPSC technology we provide a generally applicable solution to this key problem by generating isogenic pairs of disease and control human embryonic stem cells (hESCs) and hiPSCs lines that differ exclusively at a susceptibility variant for PD by modifying a single point mutation (A53T) in the -synuclein gene. The robust capability to genetically correct disease causing point mutations in patient-derived hiPSCs represents not only a significant progress for basic biomedical research but also a major advancement towards hiPSC-based cell replacement therapies using autologous cells.
Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations.
Specimen part
View SamplesInflorescence stages 1 to 12 from mutants involved in Arabidopsis small RNA metabolism. Three biological replicates of each mutant comprising at least 9 independent plants were harvested, and the expression profiles were determined using Affymetrix ATH1 arrays. Comparisons among the sample groups allow the identification of genes regulated by small RNAs (microRNAs and siRNAs).
microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
No sample metadata fields
View SamplesEstrogen signaling and epigenetic modifications, in particular DNA methylation, are involved in regulation of gene expression in breast cancers. Here we investigated a potential regulatory cross-talk between these two pathways by identifying their common target genes and exploring potential underlying molecular mechanisms in human MCF7 breast cancer cells. Principal Findings: Gene expression profiling revealed that the expression of approximately 150 genes was influenced by both 17-estradiol (E2) and a hypomethylating agent 5-aza-2-deoxycytidine (DAC). Based on gene ontology (GO), CpG island prediction analysis and previously reported estrogen receptor (ER) binding regions, we selected six genes for further analysis (BTG3, FHL2, PMAIP1, BTG2, CDKN1A and TGFB2). GO analysis suggests that these genes are involved in intracellular signaling cascades, regulation of cell proliferation and apoptosis, while CpG island prediction of promoter regions reveals that the promoters of these genes contain at least one CpG island. Using chromatin immunoprecipitation, we show that ER is recruited to CpG islands in promoters, but neither in an E2- nor in a DAC-dependent fashion. DAC treatment reactivates the expression of all selected genes although only the promoters of BTG3 and FHL2 genes are methylated, with E2 treatment showing no effect on the methylation status of these promoters. Conclusions: We identified a set of genes regulated by both estrogen signaling and DNA methylation. However, our data does not support a direct molecular interplay of mediators of estrogen and epigenetic signaling at promoters of regulated genes.
Global identification of genes regulated by estrogen signaling and demethylation in MCF-7 breast cancer cells.
Cell line
View SamplesAcute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. In order to elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness in AQM, gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.
Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model.
Sex, Specimen part, Disease, Disease stage
View Samples10 male subjects performed ~45 min one-legged cycling and 4 x 7 maximal concentric-eccentric knee extensions for each leg 15 min later. Thus, one limb performed aerobic and resistance exercise (AE+RE), while the opposing leg did resistance exercise only (RE). Biopsies were obtained from m. vastus lateralis of each leg 3 h after the resistance exercise bout.
Aerobic exercise augments muscle transcriptome profile of resistance exercise.
Sex, Specimen part, Treatment, Subject
View SamplesMitotic entry is accompanyed by the expression of a cluster of so called mitotic genes, whose activation is critical for mitosis in human and yeast cells. We found a link between the transcription machinery and cell cycle control network at mitosis in fission yeast, involving the Cdk8 kinase dependent phosphorylation of the fork head transcription factor Fkh2. We have generated a non-phosphorylatable fkh2 mutant (fkh2-S2A) also.
Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast.
No sample metadata fields
View SamplesDrugMatrix is a comprehensive rat toxicogenomics database and analysis tool developed to facilitate the integration of toxicogenomics into hazard assessment. Using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development.
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.
Sex, Specimen part, Compound, Time
View SamplesDrugMatrix is a comprehensive rat toxicogenomics database and analysis tool developed to facilitate the integration of toxicogenomics into hazard assessment. Using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development.
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.
Specimen part, Compound, Time
View SamplesDrugMatrix is a comprehensive rat toxicogenomics database and analysis tool developed to facilitate the integration of toxicogenomics into hazard assessment. Using the whole genome and a diverse set of compounds allows a comprehensive view of most pharmacological and toxicological questions and is applicable to other situations such as disease and development.
Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.
Sex, Specimen part, Compound, Time
View Samples