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GSE15930
Mus musculus
20 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Differentiation of naive CD8 T cells into cytotoxic effector cells requires three distinct signals- antigen (signal 1), costimulation -B7-1 (signal 2) and cytokine, either interleukin-12 or interferon-a/b (signal 3). Interaction of naive CD8 T cells with antigen and B7-1 programs cell division and proliferation whereas the presence of cytokines- IL-12 or IFNa/b promote survival, differentiation and memory establishment. In the absence of signal 3, the cells interacting with antigen/B7-1 undergo tolerance induction. The objective of this study was to elucidate the mechanisms how the provision of signal 3 promotes differentiation and averts tolerance induction in CD8 T cells. Trichostatin A is a pharmacological agent that inhibits histone deacetylase activity, hence regulating chromatin structure and gene expression and differentiation in many cell types. Gene signature profiles of IL-12, IFNa/b and trichostatin A stimulated cells were compared to elucidate the molecular mechanisms of gene regulation.
Publication Title
Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 73 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Erythropoiesis in mammals replenishes the circulating red blood cell (RBC) pool from hematopoietic stem/progenitor cells (HSPCs). Two distinct erythropoietic programs have been described. In the first trimester, hematopoietic precursors in the fetal yolk sac follow a primitive pattern of erythropoiesis. However, in the second trimester, hematopoietic stem cells (HSCs) from the fetal liver and later from the bone marrow differentiate by a definitive program of erythropoiesis to yield enucleated erythrocytes. RBCs can also be derived from human induced pluripotent stem cells (hiPSCs) and can express many of the red cell proteins required for normal erythrocyte function, presaging in vitro RBC production for clinical use. However, expansion and enucleation from hiPSCs is less efficient than with erythroblasts (EBs) derived from adult or cord blood progenitors. We hypothesized that substantial differential gene expression during erythroid development from hiPSCs compared to that from adult blood or cord blood precursors could account for these hitherto unexplained differences in proliferation and enucleation. We have therefore grown EBs from human adult and cord blood progenitors and from hiPSCs. Gene expression during erythroid culture from each erythroblast source was analyzed using algorithms designed to cluster co-expressed genes in an unsupervised manner and the function of differentially expressed genes explored by gene ontology. Using these methods we identify specific patterns of gene regulation for adult- and cord- derived EBs, regardless of the medium used, that are substantially distinct from those observed during the differentiation of EBs from hiPSC progenitors which largely follows a pattern of primitive erythropoiesis.
Publication Title
Distinct gene expression program dynamics during erythropoiesis from human induced pluripotent stem cells compared with adult and cord blood progenitors.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 28 Downloadable Samples
Affymetrix Chicken Gene 1.0 ST Array (chigene10st), Affymetrix Chicken Genome Array (chicken)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 16 Downloadable Samples
- Affymetrix Chicken Gene 1.0 ST Array (chigene10st)
Description
To identify markers associated with inherent cellular sex-identity, we analysed cultured macrophages from male and female chick embryos. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages. To determine whether these differences resulted from the actions of gonadal hormones, we induced gonadal sex-reversal to alter the hormonal environment of the developing chick and analysed different tissues and macrophages from male and female embryos.
Publication Title
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sample Metadata Fields
Sex, Specimen part
View Samples- Gallus gallus
- 12 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
To identify markers associated with inherent cellular sex-identity, we analysed macrophages from newly-hatched chicks. We found that male and female macrophages respond differently to stimulation by bacterial lipopolysaccharide and that female macrophages constitutively express higher levels of interferon target genes than male macrophages.
Publication Title
Cell-autonomous sex differences in gene expression in chicken bone marrow-derived macrophages.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Bulk RNA sequencing data from neural progenitor cells under conditions of low or high growth factor and Notch pathway activation Overall design: Cells were treated with high (20 ng/ml EGF and FGF) or low (0.5 ng/ml EGF) recombinant growth factors, with or without Notch pathway inhibitor (DAPT, 10 uM) for 12h.
Publication Title
<i>Cis-</i>activation in the Notch signaling pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Understanding the pattern of gene expression and identifying the specific genes expressed during erythropoiesis is crucial for a synthesis of erythroid developmental biology. Here we have isolated four distinct populations of erythroblasts at successive erythropoietin-dependent stages of erythropoiesis including the terminal, pyknotic stage. The transcriptome has been determined using Affymetrix arrays. First, we show that cells sorted by surface expression profile express not only significantly fewer genes than unsorted cells, but also significantly more differences in the expression levels of particular genes between stages than unsorted cells, demonstrating the importance of working with defined cell populations to identify lineage and temporally-specific patterns of gene expression. Second, using standard software and matched filtering we identify eleven differentially regulated genes and one continuously expressed gene previously undetected in erythroid expression studies with unknown roles in erythropoiesis (CA3, CALB1, CTSL2, FKBP1B, GSDMB, ITLN1, LIN7B, RRAD, RUNDC3A, UNQ1887, ZNF805, MYL12B). Finally, using transcription factor binding site analysis we identify potential transcription factors that may regulate gene expression during terminal erythropoiesis. Our stringent lists of differentially regulated and continuously expressed transcripts are a resource for functional studies of erythropoietic protein function and gene regulation.
Publication Title
Global gene expression analysis of human erythroid progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 426 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of the present study was to characterize the gene expression profile of the phosphodiesterase-4 inhibitor CHF6001 on top of inhaled triple therapy in sputum cells and whole blood of chronic bronchitis patients. Samples for analyses were collected from a multicenter, three-period, three-way, placebo-controlled, double-blind, complete block crossover study. Eligible patients underwent three, 32-day treatment periods during which they received CHF6001 800 or 1600 µg twice daily (total daily doses of 1600 or 3200 µg) or matching placebo, all via multi-dose dry-powder inhaler (NEXThaler). Treatment periods were separated by a 28–42 day washout. Eligible patients were male or female, ≥40 years of age, current or ex-smokers with a smoking history ≥10 pack-years, a diagnosis of COPD, post-bronchodilator forced expiratory volume in 1 second (FEV1) ≥30% and <70% predicted, ratio of FEV1 to forced vital capacity (FVC) <0.70, COPD Assessment Test score ≥10, and a history of chronic bronchitis (defined as chronic cough and sputum production for more than three months per year for at least two years) and treated with inhaled triple ICS/LABA/LAMA therapy for at least two months prior to enrollment. CHF6001 had no effect in blood, but a strong effect in sputum with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-value adjusted for False Discovery Rate<0.05) for 800 and 1600µg , respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (>87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumor necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. In conclusion inhaled PDE4-Inhibition by CHF6001 on top of triple therapy in patients with chronic bronchitis patients significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimizing unwanted systemic class-effects
Publication Title
Sputum and blood transcriptomics characterisation of the inhaled PDE4 inhibitor CHF6001 on top of triple therapy in patients with chronic bronchitis.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Analysis of early and late changes in the mouse peritoneal cells in response to E. coli induced sepis. Result provide an insight into the molecular function and pathways expressed at these different time points.
Publication Title
Transcriptomic analysis of peritoneal cells in a mouse model of sepsis: confirmatory and novel results in early and late sepsis.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
C2C12 cells expressing constitutively active hN1?ECD were activated by complete DAPT washout for 1h or 6h, or left in 10 uM DAPT Overall design: 2 Samples and 1 Control
Publication Title
Dynamic Ligand Discrimination in the Notch Signaling Pathway.
Sample Metadata Fields
Specimen part, Subject
View Samples