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SRP041955
Homo sapiens
40 Downloadable Samples
IlluminaHiSeq2000
Description
The use of low quality RNA samples in whole-genome gene expression profiling remains controversial. It is unclear if transcript degradation in low quality RNA samples occurs uniformly, in which case the effects of degradation can be normalized, or whether different transcripts are degraded at different rates, potentially biasing measurements of expression levels. This concern has rendered the use of low quality RNA samples in whole-genome expression profiling problematic. Yet, low quality samples are at times the sole means of addressing specific questions – e.g., samples collected in the course of fieldwork.
Publication Title
RNA-seq: impact of RNA degradation on transcript quantification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of contribution of cell type of origin and individual to gene expression differences in iPSCs. The hypothesis tested in the present study was that cell type of origin affects iPSC gene expression. Results show that individual has a much stronger effect than cell type of origin on differences between iPSCs derived from multiple individuals.
Publication Title
Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB
Publication Title
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them good sources of cells for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a systematic study over more than 100continuous passages to identify characteristics of culture conditions (including passage method, substrate, and media type) that influence the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. The predominant effects we observed were increased genetic instability with enzymatic passage, higher cell proliferation with feeder-free substrate, and variations among cultures in global gene expression and DNA methylation with time in culture. We observed recurrent duplications in two genomic regions that have been noted in earlier studies to be hotspots for duplication in hPSCs, as well as a previously unreported recurrent deletion of the tumor suppressor gene TP53 in all but one of the long-term culture conditions; the exception was the condition using mechanical passaging on feeder layers. The deletion of TP53 is associated with decreased mRNA expression of TP53, as well as alterations in the expression of several other genes in the TP53 pathway, which taken together indicate a decrease in the function of the TP53 pathway. Our results highlight the need for careful assessment of effects of culture conditions on cells intended for clinical therapies.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Cell line
View Samples- Mus musculus
- 90 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These studies address temporal changes in gene expression during spontaneous sleep and extended wakefulness in the mouse cerebral cortex, a neuronal target for processes that control sleep; and the hypothalamus, an important site of sleep regulatory processes. We determined these changes by comparing expression in sleeping animals sacrificed at different times during the lights on period, to that in animals sleep deprived and sacrificed at the same diurnal time.
Publication Title
Macromolecule biosynthesis: a key function of sleep.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Peroxisome proliferator-activated receptor alpha (PPAR) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPAR target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPAR in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPAR activity. In addition, activation of mouse PPAR regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPAR, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPAR agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPAR and that plasma vanin activity could serve as a readout of changes in PPAR activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
Publication Title
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 754 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Heritable genetic variants modify cystic fibrosis (CF) clinical phenotypes, e.g., lung disease, age-of-onset of persistent Pseudomonas aeruginosa (P. aeruginosa), and meconium ileus (MI). Previous genome wide association studies (GWAS) have begun to inform the genetic architecture of CF phenotypes. Analyses of gene expression will complement GWAS, as demonstrated by analyses of gene expression in lymphoblastoid cell lines (LCLs) to identify disease-related pathophysiological processes for non-CF complex traits. In this study, global gene expression was measured in RNA from LCLs from 754 CF patients and analyzed for association with lung disease severity, age-of-onset of persistent P. aeruginosa pulmonary infection, and MI at birth. Each phenotype displayed distinct expression associations. Most pathways significantly associated with lung disease were related to membranes, vesicle traffic, and Golgi/endoplasmic reticulum (ER). Pathways containing HLA genes (Class I and II) were significantly associated with both lung and P. aeruginosa phenotypes, but they displayed qualitative differences between phenotypes. MI associated with pathways involving oxidative phosphorylation. The results support the concept that gene expression associated with heritable variation acts to modify phenotypes in CF.
Publication Title
Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes.
Sample Metadata Fields
Sex
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plant cells contain different O-acetylserine(thiol)lyase (OASTL) enzymes involved in Cys biosynthesis and located in different subcellular compartments. These enzymes are made up of a complex variety of isoforms resulting in different subcellular Cys pools. To unravel the contribution of cytosolic Cys to plant metabolism, we characterized the knockout oas-a1.1 and osa-a1.2 mutants, deficient in the most abundant cytosolic OASTL isoform in Arabidposis thaliana. Total intracellular Cys and glutathione concentrations were reduced, and the glutathione redox state was shifted in favour of its oxidized form. Interestingly, the capability of the mutants to chelate heavy metals did not differ from that of the wild type, but the mutants have an enhanced sensitivity to Cd. With the aim of establishing the metabolic network most influenced by the cytosolic Cys pool, we used the ATH1 GeneChip for evaluation of differentially expressed genes in the oas-a1.1 mutant grown under non-stress conditions. The transcriptomic footprints of mutant plants had predicted functions associated with various physiological responses that are dependent on reactive oxygen species and suggested that the mutant was oxidatively stressed. To further elucidate the specific function(s) of the OAS-A1 isoform in the adaptation response to cadmium we extended the trasncriptome experiment to the wild type and oas-a1.1 mutant plants exposed to Cd. The comparison of transcriptomic profiles showed a higher proportion of genes with altered expression in the mutant than in the wild type, highlighting up-regulated genes identified as of the general oxidative stress response rather than metal-responsive genes.
Publication Title
Knocking out cytosolic cysteine synthesis compromises the antioxidant capacity of the cytosol to maintain discrete concentrations of hydrogen peroxide in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples