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GSE3854
Drosophila melanogaster
53 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
An important but largely unmet challenge in understanding the mechanisms that govern formation of specific organs is to decipher the complex and dynamic genetic programs exhibited by the diversity of cell types within the tissue of interest. Here, we use an integrated genetic, genomic and computational strategy to comprehensively determine the molecular identities of distinct myoblast subpopulations within the Drosophila embryonic mesoderm at the time that cell fates are initially specified. A compendium of gene expression profiles was generated for primary mesodermal cells purified by flow cytometry from appropriately staged wild-type embryos and from twelve genotypes in which myogenesis was selectively and predictably perturbed. A statistical meta-analysis of these pooled datasetsbased on expected trends in gene expression and on the relative contribution of each genotype to the detection of known muscle genesprovisionally assigned hundreds of differentially expressed genes to particular myoblast subtypes. Whole embryo in situ hybridizations were then used to validate the majority of these predictions, thereby enabling true positive detection rates to be estimated for the microarray data. This combined analysis reveals that myoblasts exhibit much greater gene expression heterogeneity and overall complexity than was previously appreciated. Moreover, it implicates the involvement of large numbers of uncharacterized, differentially expressed genes in myogenic specification and subsequent morphogenesis. These findings also underscore a requirement for considerable regulatory specificity for generating diverse myoblast identities. Finally, to illustrate how the developmental functions of newly identified myoblast genes can be efficiently surveyed, a rapid RNA interference assay that can be scored in living embryos was developed and applied to selected genes. This integrated strategy for examining embryonic gene expression and function provides a substantially expanded framework for further studies of this model developmental system.
Publication Title
An integrated strategy for analyzing the unique developmental programs of different myoblast subtypes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival.
Publication Title
Differentiation of CD8 memory T cells depends on Foxo1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Urothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer.
Publication Title
Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 68 Downloadable Samples
Illumina HiSeq 2500
Description
Concerted efforts over past decades have established a thorough understanding of the canonical somatic DNA methylation landscape as well as its systematic misregulation across most human cancers. However, the underlying mechanism that directs this genome-scale transformation remains elusive, with no clear model for its acquisition or understanding of its potential developmental utility. Here we present base pair resolution analysis of global remethylation from the hypomethylated state of the preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions: while the proximal epiblast establishes a canonical CpG-density dependent pattern found in somatic cells, the extraembryonic epigenome becomes substantially more mosaic. Moreover, this alternate pattern includes specific de novo methylation of hundreds of CpG island promoter containing genes that function in early embryonic development and are orthologously methylated across an extensive cohort of human cancers. From these data, we propose a model where the evolutionary innovation of extraembryonic tissues in eutherian mammals required cooption of DNA methylation-based suppression as an alternate pathway to the embryonically utilized Polycomb group proteins, which otherwise coordinate germ layer formation in response to extraembryonic cues at the onset of gastrulation. Moreover, we establish that this decision is made deterministically downstream of the promiscuously utilized, and frequently oncogenic, FGF signaling pathway and utilizes a novel combination of epigenetic cofactors. Recruitment of this silencing mechanism to developmental genes during cancer therefore reflects the misappropriation of an innate regulatory pathway that may be spontaneously sampled as an alternate epigenetic landscape within somatic cells. Overall design: Comparison of gene expression patterns in Extraembryonic Ectoderm and cancer
Publication Title
Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer.
Sample Metadata Fields
Treatment, Subject
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Study on selective vulnerability of certain brain regions to oxidative stress. Here we selected 4 brain regions (hippocampal CA1 and CA3, cerebral cortex, and cerebellar granular layer) to study this phenomenon.
Publication Title
Genomic and biochemical approaches in the discovery of mechanisms for selective neuronal vulnerability to oxidative stress.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Recent genome-wide association studies (GWAS) have identified a number of novel genetic associations with complex human diseases. In spite of these successes, results from GWAS generally explain only a small proportion of disease heritability, an observation termed the missing heritability problem. Several sources for the missing heritability have been proposed, including the contribution of many common variants with small individual effect sizes, which cannot be reliably found using the standard GWAS approach. The goal of our study was to explore a complementary approach, which combines GWAS results with functional data in order to identify novel genetic associations with small effect sizes. To do so, we conducted a GWAS for lymphocyte count, a physiologic quantitative trait associated with asthma, in 462 Hutterites. In parallel, we performed a genome-wide gene expression study in lymphoblastoid cell lines (LCLs) from 96 Hutterites. We found significant support for genetic associations using the GWAS data when we considered variants near the 193 genes whose expression levels across individuals were most correlated with lymphocyte counts. Interestingly, these variants are also enriched with signatures of an association with asthma susceptibility, an observation we were able to replicate. The associated loci include genes previously implicated in asthma susceptibility, as well as novel candidate genes enriched for functions related to T cell receptor signaling and ATP synthesis. Our results, therefore, establish a new set of asthma susceptibility candidate genes. More generally, our observations support the notion that many loci of small effects influence variation in lymphocyte count and asthma susceptibility.
Publication Title
The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes.
Sample Metadata Fields
Sex
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Powdery mildew, caused by the fungus Blumeria graminis (DC) Speer, is one of the most important foliar diseases of cereals worldwide. It is an obligate biotrophic parasite, colonising leaf epidermal cells to obtain nutrients from the plant cells without killing them. Syringolin A (sylA), a circular peptide secreted by the phytopathogenic bacterium Pseudomonas syringae pv. syringae, triggers a hypersensitive cell death reaction (HR) at infection sites when sprayed onto powdery mildew infected wheat which essentially eradicates the fungus. The rational was to identify genes whose expression was specifically regulated during HR, i.e. genes that might be involved in the switch of compatibility to incompatibility.<br></br>Powdery mildew-infected or uninfected plants were treated with syringolin two days after infection and plant material for RNA extraction was collected at 0.5, 1, 2, 4, 8, 12 hours after treatment (hat), resulting in an early (2 and 4 hat) and late pool (8 and 12 hat). Plant material that was uninfected prior to syringolin treatment was collected 8 and 12 hat (late pool of uninfected plant material), and 1 hat, respectively.
Publication Title
Transcriptional changes in powdery mildew infected wheat and Arabidopsis leaves undergoing syringolin-triggered hypersensitive cell death at infection sites.
Sample Metadata Fields
Compound, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
BACKGROUND: miRNA have been shown to play an important role during immune-mediated diseases such as inflammatory bowel disease. The aim of this study was to assess differential expression of miRNA between uninfected and infected mice with Clostridium difficile strain VPI 10463 RESULTS: MicroRNA (miRNA)-sequencing analysis indicated that miR-146b, miR-1940, and miR-1298 were significantly overexpressed in colons of C. difficile-infected mice Overall design: Colon of uninfected and C.difficile-infected C57BL6/J WT mice were sampled at day 4 post-infection with Clostridium difficile VPI 10463. The infection dose was 107 cfu/mouse.
Publication Title
Modeling the role of peroxisome proliferator-activated receptor γ and microRNA-146 in mucosal immune responses to Clostridium difficile.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Illumina Genome Analyzer
Description
Development, growth and adult survival are coordinated with available metabolic resources. The insulin/IGF and TOR signaling pathways relay nutritional status, thereby ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21-23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is down-regulated with age. This miRNA controls branched-chain amino acid (BCAA) catabolism and the activity of the TOR kinase, a central growth regulator. Metabolite analysis suggests that the mechanistic basis may be an accumulation of BCKAs, rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g. translational fidelity. Constitutive miR-277 expression as well as transgenic inhibition with a miRNA sponge construct shortens lifespan. Furthermore, constitutive miR-277 expression is synthetically lethal with reduced insulin signaling. Thus, optimal metabolic adaptation requires tuning of cellular BCAA catabolism by miR-277 to be concordant with systemic growth signaling. Overall design: Transgenic Drosophila melanogaster fruitflies carrying strong, ubiquitously expressed pre-miR277 hairpins (wt and two mutant versions) were dissected, total RNA was extracted from the abdomen and gel-purified for size selection (~18-30 nt). Digested plasmid samples were compared to those of circular plasmids and a nontransfected control. The purpose of this experiment was to demonstrate the extent of expression from mutant pre-miR277 hairpins, mut1 should abolish Drosha-processing while mut2 is conservative.
Publication Title
Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 55 Downloadable Samples
Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Sample Metadata Fields
Specimen part
View Samples