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GSE5525
Arabidopsis thaliana
14 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA) and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, P. rapae, and F. occidentalis, more than 50% were also induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker-specific. All together our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.
Publication Title
Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 45 Downloadable Samples
Illumina HiSeq 2500
Description
As RIG-I activation induces potent IFN-I responses,we analyzed the role of IFN-I in intestinal tissue protection and prevention of GVHD. We performed RNA sequencing with tissue samples from SI of WT mice that received TBI -/+ previous 3pRNA treatment and -/+ antibody-mediated blockade of IFNAR. Application of 3pRNA before TBI resulted in a significant increase of IFN-inducible genes in the SI as compared to solely irradiated mice. Blockade of IFNAR signaling abrogated 3pRNA-mediated up-regulation of IFN-induced genes, demonstrating that RIG-I-induced gene-regulation depends on IFN-I. Overall design: Balb/c mice were solely irradiated (9Gy) (n=3), pretreated with Rig-I agonist 3pRNA prior (d-1) to irradiation (n=3) or pre-treated with 3pRNA (d-1) + anti-IFNaR1 blocking antibody (d-2) prior to irradiation (n=3). RNA from small intestines was isolated 12h after irradiation and used for RNA sequencing.
Publication Title
RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Enhanced prenatal fatty streak formation in human fetuses has been associated with maternal hypercholesterolemia. However, the possible roles of maternal genetic background and in utero environment on development of atherosclerosis in adult life have not been unraveled. We generated genetically identical heterozygous apoE-deficient mice offspring with a different maternal background to study the intrauterine effect of maternal genotype and associated hypercholesterolemia on the developing vascular system. As read out for increased atherosclerosis development in adult life, a constrictive collar was placed around the carotid artery to induce lesion formation. A significant increase in endothelial cell activation and damage was detected in the carotid arteries of heterozygous apoE-deficient fetuses with apoE-deficient mothers compared with offspring from wild type mothers, but no fatty streak formation was observed. Postnatally, all carotid arteries revealed normal morphology. In adult offspring with maternal apoE-deficiency, the constrictive collar resulted in severe lesion (9/10) development compared with no to only minor lesions (2/10) in offspring of wild type mothers. Microarray analysis showed no effect of maternal apoE-deficiency on gene expression in adult offspring. We conclude that maternal apoE-deficiency not only affects fetal arteries, but also increases the susceptibility for development of collar-induced atherosclerosis in adult life.
Publication Title
Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 47 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Closure or patency of the ductus arteriosus is a critical event in neonatal life. We aimed to identify genes that are specifically expressed in the ductus arteriosus versus (the non-closing) aorta
Publication Title
Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The leg of healthy volunteers was locally deconditioned using three weeks of unilateral lower limb suspension (ULLS). The extremely deconditioned legs of subjects with a spinal cord injury (SCI) were trained using eight weeks of functional electrical stimulation (FES) exercise, 2-3 times per week (total 20 sessions).
Publication Title
Expression of genes involved in fatty acid transport and insulin signaling is altered by physical inactivity and exercise training in human skeletal muscle.
Sample Metadata Fields
Subject, Time
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal. Overall design: RNA seq in Drosophila melanogaster (flies) (3 Conditions, triplicates)
Publication Title
m<sup>6</sup>A modulates neuronal functions and sex determination in Drosophila.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Naturally occurring CD25+CD4+ regulatory T cells (T reg cells) are currently intensively characterized because of their major importance in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy. Originally, CD4+ T reg cells were identified exclusively by the constitutive expression of CD25, and many in vivo experiments have been performed using depleting antibodies directed against CD25. However, both the existence of CD25 T reg cells, especially within peripheral tissues, as well as the expression of CD25 on activated conventional T cells, which precludes discrimination between T reg cells and activated conventional T cells, limits the interpretation of data obtained by the use of anti-CD25 depleting antibodies. The most specific T reg cell marker currently known is the forkhead box transcription factor Foxp3, which has been shown to be expressed specifically in mouse CD4+ T reg cells and acts as a master switch in the regulation of their development and function. To address the question of the in vivo role of T reg cells in immunopathology, we have generated bacterial artificial chromosome (BAC)transgenic mice termed depletion of regulatory T cell (DEREG) mice, which express a diphtheria toxin receptor (DTR) enhanced GFP (eGFP) fusion protein under the control of the foxp3 locus, allowing both detection and inducible depletion of Foxp3+ T reg cells. The gene expression profile of both CD4+eGFP+FoxP3+ and CD4+eGFPnegFoxP3neg cells isolated from DEREG mice was here analyzed by micro array.
Publication Title
Immunostimulatory RNA blocks suppression by regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 149 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A previously predictive CEBPA double mutant (CEBPAdm) signature was hampered by the recently reported CEBPA silenced AML cases that carry a similar gene expression profile (GEP). Two independent AML cohorts were used to train and evaluate the predictive value of the CEBPAdm signature in terms of sensitivity and specificity. A predictive signature was created, containing 25-probe sets by using a logistic regression model with Lasso regularization, which selects discriminative probe sets between the classes, CEBPAdm and all other AML cases, CEBPA wild type (CEBPAwt) and CEBPA single mutant (CEBPAsm). Subsequently, a classifier was trained on the entire HOVON-SAKK cohort based on a two-class approach; CEBPAdm versus all other cases (CEBPAwt and CEBPAsm). This trained classifier subsequently classified 16 candidate CEBPAdm cases in the AMLSG-cohort out of 154 AML cases. This approach showed perfect sensitivity and specificity (both 100%). In addition, we have performed a classification between CEBPAdm ,CEBPAsm, and CEBPAwt to infer if we were able to accurately classify CEBPAsm cases. We observed that all CEBPAsm cases were classified as CEBPAwt, thus CEBPAsm cases do not have a consistent gene expression pattern and are different from the CEBPAdm group.
Publication Title
Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 116 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stem cell gene expression programs influence clinical outcome in human leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Experiments using xenografts show that some solid tumours and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSC). Despite promise, the relevance of the CSC model to human disease remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model based on sorting multiple populations from each of 16 primary human AML samples and identifying which contain leukemia stem cells (LSC) using a sensitive xenograft assay. Analysis of gene expression from all functionally validated populations yielded an LSC-specific signature. Similarly, a hematopoietic stem cell (HSC) gene signature was established. Bioinformatic analysis identified a core transcriptional program shared by LSC and HSC, revealing the molecular machinery underlying stemness properties. Both stem cell programs were highly significant independent predictors of patient survival and also found in existing prognostic signatures. Thus, determinants of stemness influence clinical outcome of AML establishing that LSC are clinically relevant and not mere artifacts of xenotransplantation.
Publication Title
Stem cell gene expression programs influence clinical outcome in human leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples