This SuperSeries is composed of the SubSeries listed below.
Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.
Sex, Age
View SamplesAnalysis 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.
Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs.
Sex, Age
View SamplesInduced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. Here we investigate the use of iPSCs and iPSC-derived cells to study the impact of genetic variation across different cell types and as models for the genetics of complex disease. We established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring RNA, chromatin accessibility and DNA methylation. Regulatory variation between individuals is lower in iPSCs than in the differentiated cell types, consistent with the intuition that developmental processes are generally canalized. While most cell-type- specific regulatory effects lie in chromatin that is open only in the affected cell-types, we find that 20% of cell-type specific effects are in shared open chromatin. Finally, we developed deep neural network models to predict open chromatin regions in these cell types from DNA sequence alone and were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on tissue-specific chromatin accessibility. Our results provide a framework for using iPSC technology to study regulatory variation in cell types that are otherwise inaccessible. Keywords: Expression profiling by high throughput sequencing Overall design: Immortalized lymphoblastoid cell lines from 58 African individuals were reprogrammed into induced pluripotent stem cells
Impact of regulatory variation across human iPSCs and differentiated cells.
Specimen part, Subject
View SamplesAcute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcriptional regulator Aire binds to and activates super-enhancers.
Sex, Age, Specimen part, Treatment
View SamplesMicroarray profiles of MECs from mice treated with topoisomerase inhibitors
The transcriptional regulator Aire binds to and activates super-enhancers.
Sex, Age, Treatment
View SamplesHigh quality RNA was extracted from the whole seedlings (Combined root and leaf samples) using TRI Reagent (Ambion, Inc. USA) and pooled from 12 independent stressed and non-stressed plant samples separately, and treated with DNase-I (QIAGEN GmbH, Germany). Subsequently, RNA cleanup was carried out using RNeasy Plant Mini Kit (QIAGEN GmbH, Germany) and 5 ug of total RNA from each sample in triplicates were reverse-transcribed to double stranded cDNA using the GeneChipᆴ One-Cycle cDNA Synthesis Kit. The biotin-labelled cRNA was made using the GeneChipᆴ IVT Labelling Kit (Affymetrix, CA, USA). Twenty microgram of cRNA samples was fragmented and out of which which 7.5 ug cRNA were hybridized for 16 hours at 45C to the Affymetrix GeneChipᆴ Rice Genome Array (Santa Clara, CA, USA). After washing and staining with R-phycoerythrin streptavidin in a Fluidics Station, using the Genechipᆴ Fluidics Station 450, the arrays were scanned by the Genechipᆴ 3000 Scanner. The chip images were scanned and extracted using default settings and the CEL files were produced with the Affymetrix GeneChip Operating Software (GCOS 1.2). The resulting .CEL files were imported into the GeneSpring GX 10 (Agilent Technologies Inc, Santa Clara CA) and normalized with the PLIER16 algorithm. The resulting expression values were log2-transformed. Average log signal intensity values of three technical replicates for each sample were used for advance analysis.
Comparative analysis of drought-responsive transcriptome in Indica rice genotypes with contrasting drought tolerance.
Specimen part
View SamplesVS94 gene expression at different time-points in SAPI medium in absence and presence of AI-2 was studied.
Temporal regulation of enterohemorrhagic Escherichia coli virulence mediated by autoinducer-2.
No sample metadata fields
View SamplesFor the microarray experiments, 10 g glass wool (Corning Glass Works, Corning, N.Y.) were used to form biofilms (30) in 250 mL in 1 L Erlenmeyer shake flasks which were inoculated with overnight cultures diluted that were 1:100. For EHEC with 7-hydroxyindole and isatin, 1000 mM 7-hydroxyindole in 250 mL DMF, 250 mM isatin in 250 mL DMF, or 250 mL DMF alone were added to cells grown in LB. The cells were shaken at 250 rpm and 30C for 7 hours to form biofilms on the glass wool, and RNA was isolated from the suspension cells and the biofilm.
Enterohemorrhagic Escherichia coli biofilms are inhibited by 7-hydroxyindole and stimulated by isatin.
No sample metadata fields
View SamplesPro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-B dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-B activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-B target gene-expressions and suppressing apoptotic cellular death independent of principal NF-B subunit RelA. We further demonstrate that activating mutations in non-canonical NF-B module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-B response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-B system and its potential involvement in human neoplasm.
Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.
Specimen part, Treatment
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