Expression data from different brain regions of mice
Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.
Specimen part
View SamplesWe report changes in the levels of gene expression between 48hpf hearts and 56hpf hearts, the initial stages of valvulogenesis Overall design: 48hpf and 56hpf hearts were dissected and RNA was extracted. RNA profiles were then generated at each stage using Illumina deep sequencing
klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis.
No sample metadata fields
View SamplesdeepCAGE was used in conjunction with Pacific Biosciences Iso-Seq and Illumina RNA-Seq to globally resolve transcript structures in replicating Epstein-Barr virus. Overall design: deepCAGE of replicating Epstein-Barr virus in Akata cells to identify transcript 5'' ends
Global transcript structure resolution of high gene density genomes through multi-platform data integration.
Specimen part, Subject
View SamplesTight regulation of hematopoietic stem cell (HSC) homeostasis is essential for life-long hematopoiesis, for preventing blood cancers and for averting bone marrow failure. The underlying mechanisms are incompletely understood. Here, we identify production of inositol-tetrakisphosphate (IP4) by inositoltrisphosphate 3-kinase B (ItpkB) as essential for HSC quiescence and function. Young ItpkB-/- mice accumulated phenotypic HSC and showed extramedullary hematopoiesis. ItpkB-/- HSC were less quiescent and proliferated more than wildtype controls. They downregulated quiescence and stemness associated mRNAs, but upregulated activation, oxidative metabolism, protein synthesis and lineage associated transcripts. Although they showed no significant homing defects, ItpkB-/- HSC had a severely reduced competitive long-term repopulating potential. Aging ItpkB-/- mice lost hematopoietic stem and progenitor cells and died with severe anemia. Wildtype HSC normally repopulated ItpkB-/- hosts, incidating a HSC-intrinsic ItpkB requirement. ItpkB-/- HSC had reduced cobblestone-area forming cell activity in vitro and showed increased stem-cell-factor activation of the phosphoinositide 3-kinase (PI3K) effector Akt, reversed by exogenous provision of the known PI3K/Akt antagonist IP4. They also showed transcriptome changes consistent with hyperactive Akt/mTOR signaling. Thus, we propose that ItpkB ensures HSC quiescence by limiting cytokine-induced PI3K signaling in HSC. Overall design: For each of 3 replicate ItpkB-/- or wt samples, we enriched Lin- cells from BM of 4 pooled age-matched mice with Rapidspheres (Stemcell Technologies), FACS-sorted =10,000 LSK CD34-CD150+CD48-Flk2- LT-HSC into lysis buffer and prepared RNA with RNeasy Micro kits (Quiagen). RNA sequencing was done using an Illumina HISeq Analyzer 2000, Casava v1.8.2 genome analyzer pipeline, TopHat v1.4.1/Bowtie2 genome alignment and Partek v6.6 mRNA annotation software. Statistical analyses were done with edgeR (Bioconductor package), excluding genes with false discovery rates >0.15, fold-change magnitudes =1.4 and log2(counts per million) =4 to avoid undefined values and the poorly defined log fold-changes for low counts close to 0. Unsupervised clustering of 441 significantly changed genes was done with dChip using rank correlation and a centroid linkage method. Scatter plots were generated in Spotfire. GSEA was performed with gene set permutation, using gene sets from MSigDB (www.broadinstitute.org/gsea/msigdb/index.jsp) or manually curated from, excluding genes without HUGO approved symbols
IP3 3-kinase B controls hematopoietic stem cell homeostasis and prevents lethal hematopoietic failure in mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View SamplesThe amyloid precursor protein (APP) plays a central role in the pathogenesis of Alzheimers disease (AD). Processing of APP by - and -secretase activities results in the production of -amyloid (A), the main constituent of Alzheimer plaques, but also in the generation of the APP intracellular domain (AICD). Recently, it has been demonstrated that AICD has transactivation potential, however, the targets of AICD dependent gene regulation and hence the physiological role of AICD remain largely unknown. In this work we analysed transcriptome changes during AICD dependent gene regulation using a human neural cell culture system inducible for expression of AICD, its co-activator Fe65, or the combination of both. Induction of AICD was associated with increased expression of genes with known function in the organization and dynamics of the actin cytoskeleton as well as genes involved in the regulation of apoptosis.
Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD).
No sample metadata fields
View SamplesWe present primary results from the Sequencing Quality Control (SEQC) project, coordinated by the United States Food and Drug Administration. Examining Illumina HiSeq, Life Technologies SOLiD and Roche 454 platforms at multiple laboratory sites using reference RNA samples with built-in controls, we assess RNA sequencing (RNA-seq) performance for sequence discovery and differential expression profiling and compare it to microarray and quantitative PCR (qPCR) data using complementary metrics. At all sequencing depths, we discover unannotated exon-exon junctions, with >80% validated by qPCR. We find that measurements of relative expression are accurate and reproducible across sites and platforms if specific filters are used. In contrast, RNA-seq and microarrays do not provide accurate absolute measurements, and gene-specific biases are observed, for these and qPCR. Measurement performance depends on the platform and data analysis pipeline, and variation is large for transcriptlevel profiling. The complete SEQC data sets, comprising >100 billion reads (10Tb), provide unique resources for evaluating RNA-seq analyses for clinical and regulatory settings.
A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium.
No sample metadata fields
View SamplesHuntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. We made induced pluripotent stem cell (iPSC) lines from HD patients and controls. Though no obvious effects of the CAG expansion on reprogramming or subsequent neural stem cell (NSC) production were seen, HD-NSCs showed CAG expansion-associated gene expression patterns and, upon differentiation, changes in electrophysiology, metabolism, cell adhesion, and ultimately an increased risk of cell death for both medium and longer CAG repeat expansions, with some deficits greater in cells from longer repeat HD NSCs. The HD180 lines were more vulnerable than control lines to cellular stressors and BDNF withdrawal using a range of assays across consortium laboratories. This HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a novel human stem cell platform for screening new candidate therapeutics.
Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.
Specimen part, Disease, Disease stage
View SamplesWe were interested in characterizing the transcriptional changes that occur on a genome-wide scale following treatment of EGFR-mutant lung cancer cells with targeted therapies.
Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways.
Specimen part, Cell line, Treatment
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