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Mus musculus
11 Downloadable Samples
Illumina HiSeq 2500
Description
Mononuclear phagocytes are a diverse cell family that occupy all tissues and assume numerous functions to support tissue and systemic homeostasis. Our ability to investigate the roles of individual subsets is limited by an absence of approaches to ablate gene function within specific sub-populations. Using Nr4a1-dependent Ly6Clow monocytes as a representative cell type we show that enhancer deletion addresses these limitations. Combining ChIP-Seq and molecular approaches we identify a single, conserved, sub-domain within the Nr4a1 enhancer that is essential for Ly6Clow monocyte development. Mice lacking this enhancer lack Ly6Clow monocytes but retain Nr4a1 gene expression in macrophages during steady state and in response to LPS. Nr4a1 is a key negative regulator of inflammatory gene expression and decoupling these processes allows Ly6Clow monocytes to be studied without confounding influences. Enhancer targeting possesses greater specificity than cre recombinase-mediated gene deletion, providing a route to generate loss-of-function models in closely related cell types. Overall design: Paired End mRNA sequencing of FACS purified primary murine MDP, cMoP, Ly6Chi and Ly6Clow monocytes from the bone marrow and Ly6Chi and Ly6Clow monocytes from the peripheral blood
Publication Title
Deleting an Nr4a1 Super-Enhancer Subdomain Ablates Ly6C<sup>low</sup> Monocytes while Preserving Macrophage Gene Function.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
GSE64447- Mus musculus
- 19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Prospectively isolated and characerized skeletal progenitor lineages
Publication Title
Identification and specification of the mouse skeletal stem cell.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Prospectively isolated and characerized skeletal progenitor lineages
Publication Title
Identification and specification of the mouse skeletal stem cell.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 229 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
One of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
Publication Title
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
AE-expressing murine BM cells treated with all-trans retinoic acid (ATRA) in semi-solid methycellulose-based cultures show an increase in self-renewal capacity whilst treatment with a specific RARa agonist NRX195183 reduces their clonogenicity. Gene expression analysis was performed to further investigate the molecular mechanisms underlying these observations. Upregulated gene sets were identified in the ATRA-treated AE BM cells.
Publication Title
ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Danio rerio
- 54 Downloadable Samples
- IlluminaHiSeq2000
Description
Development is a complex and well-defined process characterized by rapid cell proliferation and apoptosis. At this stage in life, a developmentally young organism is more sensitive to toxicants and other stressors when compared to an adult. In response to pro-oxidant exposure, members of the Cap’n’Collar (CNC) basic leucine zipper (b-ZIP) transcription factor family (including the Nfe2-related factors, Nrfs) activate the expression of genes that contribute to reduced toxicity. Here, we studied the role of the Nrf protein, Nfe2, in the developmental response to pro-oxidant exposure in the zebrafish. Following acute waterborne exposures to diquat or tert-buytlhydroperoxide (tBOOH) at three developmental stages, wildtype (WT) and nfe2 knockout (KO) embryos and larvae were morphologically scored and their transcriptomes sequenced. Overall design: Wildtype animals were on the AB background and an additional germline nfe2 knockout strain were created by disruption of the nfe2 reading frame. Waterborne exposures to either diquat or tBOOH were carried out at three different developmental stages: 2 hours post fertilization (hpf), 48hpf, and 96hpf in 3 pools of 30 embryos per condition. Animals were exposed to no treatment, 20µM diquat or 1mM tBOOH for a 4-hour dosing period. Total RNA was isolated from pooled animals and 50 bp, paired end, libraries were sequenced using the Illumina HiSeq 2000 platform, with approximately 25 million reads per sample. Reads were then aligned to the Ensembl GRCz10 zebrafish reference genome using Tophat2 and raw counts data normalized using DESeq2. Gene annotation was from Ensemble for GRCz10.
Publication Title
The transcription factor, Nuclear factor, erythroid 2 (Nfe2), is a regulator of the oxidative stress response during Danio rerio development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
DNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.
Publication Title
Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogen-responsive genes were identified by transcript profiling of estrogen-treated MCF-7 breast cancer cells.
Publication Title
Identification of functional networks of estrogen- and c-Myc-responsive genes and their relationship to response to tamoxifen therapy in breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differential gene expression analysis of parental and resistant sub-lines of melanoma cell lines treated or untreated with PLX4032
Publication Title
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples