Analysis of the differences between NPC derived astrocytes and Olig2PC derived astrocytes at gene expression level. Olig2PC-Astros show differences in functions and gene expression profiles from NPC-Astros in vitro, providing clues of superior neuroprotection effect of Olig2PC-astrocytes.
hESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
No sample metadata fields
View SamplesSystematic somatic mutation screening of 4000 genes in human clear cell renal cell carcinoma. Information on corresponding somatic mutations in each sample can be found at http://www.sanger.ac.uk/genetics/CGP/Studies/.
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
No sample metadata fields
View SamplesBackground
Expression quantitative trait loci mapping identifies new genetic models of glutathione S-transferase variation.
No sample metadata fields
View SamplesContext: In many cancers, specific subpopulations of cells appear to be uniquely capable of initiating and maintaining tumors. The strongest support for this cancer stem cell model comes from transplantation assays in immune-deficient mice indicating that human acute myeloid leukemia (AML) is organized as a cellular hierarchy driven by self-renewing leukemia stem cells (LSC). This model has significant implications for the development of novel therapies, but its clinical significance remains unclear.
Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia.
Disease, Disease stage, Subject
View SamplesTrichomes are specialised epidermal cells that generally play a role in reducing transpiration and act as a deterrent to herbivory. In a screen of activation tagged Populus tremula x P. alba 717-1B4 trees, we identified a mutant line, fuzzy, with increased foliar trichome density. This mutant also had a 35% increase in growth rate and a 200% increase in the rate of photosynthesis as compared to wild-type poplar. The fuzzy mutant had significant resistance to feeding by larvae of the white spotted tussock moth (Orgyia leucostigma), a generalist insect pest of poplar trees. The fuzzy phenotype is attributable to activation tagging and increased expression of the gene encoding PtaMYB186, which is related to Arabidopsis thaliana MYB106, a known regulator of trichome initiation. The fuzzy phenotype can be recapitulated by overexpressing PtaMYB186 in poplar. PtaMYB186 overexpression results in reconfiguration of the poplar transcriptome, with changes in the transcript abundance of suites of genes that are related to trichome differentiation. It is notable that this gene responsible for trichome development also altered traits related to growth rate and pest resistance, suggesting that non-intuitive facets of plant development might be useful targets for plant improvement.
Endogenous overexpression of Populus MYB186 increases trichome density, improves insect pest resistance, and impacts plant growth.
Specimen part
View SamplesBoth the mechanism of action and the factors determining the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of hippocampal neurons via enhanced serotonergic signaling, but it is still unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neurogenic effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. The behavioral and neurogenic responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis is a determinant of antidepressant efficacy.
Genetic regulation of behavioral and neuronal responses to fluoxetine.
Sex, Treatment
View Samples5''-complete cDNA sequencing on ribosome-depleted total RNA from the human K562 cell line. Provides high-quality, genome-wide single-base resolution profiling of transcription start sites and their expression levels. Overall design: This dataset represents a whole-genome, single-base resolution profiling of transcription start site (TSS) expression in the human K562 cell line. These profiles were established using RAMPAGE, a high-throughput, high-accuracy 5''-complete cDNA sequencing method implemented on the Illumina platform. The data was analyzed using custom scripts and algorithms that are all available upon request.
High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression.
Cell line, Subject
View SamplesAustism spectrum disorder (ASD) is a heterogeneous behavioral disease most commonly characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a common clinical outcome. Transcript levels of Mecp2, Mef2a, Mef2d, Fmr1, Nlgn1, Nlgn3, Pten, and Shank3 were knocked-down in mouse primary neuron cultures using shRNA/lentivirus constructs. Whole genome expression analysis was conducted for each of the knock-down cultures as well as a mock-transduced culture and a culture exposed to a lentivirus expressing luciferase. Gene set enrichment and a causal reasoning engine were employed to indentify pathway level perturbations generated by the transcript knock-down. Quantitation of the shRNA targets confirmed the successful knock-down at the transcript and protein levels of at least 75% for each of the genes. After subtracting out potential artifacts caused by transfection and viral infection, gene set enrichment and causal reasoning engine analysis showed that a significant number of gene expression changes mapped to pathways associated with neurogenesis, long-term potentiation, and synaptic activity. This work demonstrates that despite the complex genetic nature of ASD, there are common molecular mechanisms that connect many of the best established autism candidate genes. By identifying the key regulatory checkpoints in the interlinking transcriptional networks underlying autism, we are better able to discover the ideal points of intervention that provide the broadest efficacy across the diverse population of autism patients.
Transcriptomic analysis of genetically defined autism candidate genes reveals common mechanisms of action.
Specimen part, Treatment
View SamplesIn order to establish a list of candidate direct COUP-TFI gene targets in the inner ear, we analyzed the differential gene expression profiles of the wild-type and the COUP-TFI/ P0 inner ears.
Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI.
Specimen part
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