Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients by viral vector-mediated factor transduction represent a powerful tool for biomedical research and may provide a source for cell replacement therapies. However, the proviruses encoding the reprogramming factors represent a major limitation of the current technology because even low vector expression may alter the differentiation potential of the iPSCs and induce malignant transformation. Here we show that fibroblasts from five patients with idiopathic Parkinsons disease (PD) can be efficiently reprogrammed into hiPSCs and subsequently differentiated into dopaminergic neurons. Moreover, we derived PD specific hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Upon factor deletion these cells maintain a pluripotent state and intact karyotype. Importantly, these factor-free hiPSCs show a global gene expression profile, which is more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in conventional virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors.
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View SamplesPurpose: using RNA-seq as a screening tool to determine candidate genes of interest within a genetically defined neural subpopulation in the zebrafish embryonic spinal cord. Results: The early embryonic spinal cord displays patterns of spontaneous activity that generate the earliest motor behavior in the zebrafish. We show the behavior and the neural activity to be inhibited by environmental levels of light. Since at these young ages the fish is blind, and since restricted illumination patterns on the trunk of the fish can elicit a photo-response, we hypothesized that the photo-inhibition is an intrinsic property of the active central pattern generator network within the spinal cord. We FACS-isolated cells from this network as well as those from a panneuronal population and sequenced mRNAs. Through differential expression analysis we identified vertebrate ancient long opsin a as a candidate and then further validated its function in the circuit through knockdown and rescue experiments. Overall design: RNA sequencing of 2 FACS purified neural populations from zebrafish spinal cord.
A spinal opsin controls early neural activity and drives a behavioral light response.
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View SamplesPericytes are integral components of the tissue vasculature and have essential functions in tumour angiogenesis. Endosialin (CD248) is a type I transmembrane glycoprotein highly expressed on pericytes in the tumour vasculature of most solid tumours, however it is low or negligibly expressed on normal tissue pericytes. Experiments using wild-type and endosialin-knockout mice has revealed that stromal endosialin expression facilitates intravasation of tumor cells from the primary tumor into the circulation, thereby promoting metastatic dissemination.
Endosialin-Expressing Pericytes Promote Metastatic Dissemination.
Sex, Specimen part, Disease
View SamplesMicroarrays have been widely used for the analysis of gene expression and several commercial platforms are available. The combined use of multiple platforms can overcome the inherent biases of each approach, and may represent an alternative that is complementary to RT-PCR for identification of the more robust changes in gene expression profiles.
Cross platform microarray analysis for robust identification of differentially expressed genes.
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View SamplesTreatment with Aurora inhibitors has been shown to induce diverse biological responses in different tumor cell lines, in part depending on their p53 status. To characterize at the transcriptional level the effects of Danusertib we analyzed by microarray different tumor cell lines, with WT or mutant p53 status, that showed differential cell cycle response upon drug treatment.
Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of several compounds on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitors PHA-848125 and PHA-690509 on the A2780 cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitor PHA-793887 on the A2780 human adenocarcinoma ovary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitor PHA-848125 (referred to as CDK-125) on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View Samples