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Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Regulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation. Overall design: RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
Publication Title
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Heart failure (HF) is a major health and economic burden in developed countries. It has been proposed that the pathogenesis of HF may involve the action of mitochondria. Here we evaluate three different models of HF: tachycardiomyopathy, HF with preserved left ventricular (LV) ejection fraction, and LV myocardial ischemia and hypertrophy. Regardless of whether LVEF is preserved or reduced, our results indicate that the three models share common molecular features: an increase in mitochondrial ROS, followed by ultrastructural alterations in the mitochondrial cristae and loss of mitochondrial integrity that lead to cardiomyocyte death. We show that the ablation of the mitochondrial protease OMA1 averts cardiomyocyte death in all three experimental HF models, and thus, plays a direct role in cardiomyocyte protection. This finding identifies OMA1 as a potential target for preventing the progression of myocardial damage in HF associated to a variety of etiologies. Overall design: Transcriptome analysis of 12-week-old wild type mice versus OMA1 KO mice under control (non-treated) or treated with Isoproterenol chronically (implanted minipumps) for 7 days in heart tissue. The nuclear genetic background for both genotypes is C57BL/6JOlaHsd.
Publication Title
Ablation of the stress protease OMA1 protects against heart failure in mice.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the marrow and lymphatic tissues, chronic lymphocytic leukemia (CLL) cells interact with accessory cells that constitute the leukemia microenvironment. In lymphatic tissues, CLL cells are interspersed with CD68+ nurselike cells (NLC) and T cells. However, the mechanism regulating co-localization of CLL cells and these accessory cells are largely unknown. To dissect the molecular cross-talk between CLL and NLC, we profiled the gene expression of CD19-purified CLL cells before and after co-culture with NLC. NLC co-culture induced high-level expression of B cell maturation antigen (BCMA) and two chemoattractants (CCL3, CCL4) by CLL cells. Supernatants from CLL-NLC co-cultures revealed high CCL3/CCL4 protein levels. B cell receptor triggering also induced a robust induction of CCL3 and CCL4 expression by CLL cells, which was almost completely abrogated by a specific Syc inhibitor, R406. High CCL3 and CCL4 plasma levels in CLL patients suggest that activation of this pathway plays a role in vivo. These studies reveal a novel mechanism of cross-talk between CLL cells and their microenvironment, namely the secretion of two T cell chemokines by CLL-NLC interaction and in response to BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells, and thereby actively create a microenvironment that favors their growth and survival.
Publication Title
High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Chromosomal instability (CIN) is thought to be a source of mutability in human cancer. However, CIN is highly deleterious for the cell, and the resulting aneuploidy induces metabolic stress and compromises cell fitness. Here we utilized the X-chromosome dosage compensation mechanism and changes in X-chromosome number to demonstrate in Drosophila epithelial cells the causal relationship between CIN, aneuploidy, gene dosage imbalance and tumorigenesis. Whereas the harmful effects of CIN can be buffered by resetting the X-chromosome dosage compensation to compensate for changes in X-chromosome number, interfering with the mechanisms of dosage compensation suffices to induce tumorigenesis. In addition, multiple mechanisms buffer the deleterious effects of CIN including DNA-damage repair, activation of the p38 signalling pathway, and induction of cytokine expression to promote compensatory cell proliferation. These data reveal a key role of gene dosage imbalances to CIN-induced programmed cell death and tumorigenesis and the existence of robust compensatory mechanisms.
Publication Title
Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis.
Sample Metadata Fields
Specimen part
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GSE36779- Escherichia coli
- 2 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
To provide more evidence of the specificity of the RNase activity of GhoS, we performed a whole-transcriptome study for the production of GhoS vs. an empty plasmid so that we could investigate all of the cells transcripts for cleavage with GhoS, in vivo (i.e., BW25113/pCA24N-ghoS vs. BW25113/pCA24N with 1 mM IPTG induction of ghoS for 90 min). Under these conditions, only 20 genes were found to be repressed by more than 4-fold; there were no induced genes. These GhoS-repressed genes were all involved in the biosynthesis/transport of purines and pyrimidines; among them, pyrI was most highly repressed (-20 fold). These results suggest that GhoS selectively cleaves only a few cellular targets.
Publication Title
A new type V toxin-antitoxin system where mRNA for toxin GhoT is cleaved by antitoxin GhoS.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The objective of the study was to determine the cause of anovulation in transgenic mice with conditional over-activation of the hedgehog signaling pathway in the ovary. In Amhr2(cre/+)-SmoM2 transgenic mice, a constitutively active version of the hedgehog signal transducer, smoothened (SMO), known as SMOM2, is expressed in the ovary following cre-mediated recombination. The hypothesis tested is that changes in the neonatal ovary caused by over-activation of hedgehog signaling leads to the life-long anovulation phenotype in transgenic mice.
Publication Title
Overactivation of hedgehog signaling alters development of the ovarian vasculature in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gestational protein restriction is a model for low birth size. We hypothesized that taurine supplementation would protect against changes in newborn liver and muscle caused by a maternal low protein diet.
Publication Title
Gestational protein restriction in mice has pronounced effects on gene expression in newborn offspring's liver and skeletal muscle; protective effect of taurine.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To study the physiological role of WNT4 in the postnatal ovary, a mouse strain bearing a floxed Wnt4 allele was created and mated to the Amhr2tm3(cre)Bhr strain to target deletion of Wnt4 to granulosa cells. Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had significantly reduced ovary weights and produced smaller litters (P<0.05). Serial follicle counting demonstrated that, while Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice were born with a normal ovarian reserve and maintained normal numbers of small follicles until puberty, they had only 25.2% of the normal number of healthy antral follicles. Some Wnt4flox/-;Amhr2tm3(cre)Bhr/+ mice had no antral follicles or corpora lutea and underwent premature follicle depletion. RTPCR analyses of Wnt4flox/-;Amhr2tm3(cre)Bhr/+ granulosa cells and cultured granulosa cells that overexpress WNT4 demonstrated that WNT4 regulates the expression of Star, Cyp11a1 and Cyp19, steroidogenic genes previously identified as downstream targets of the WNT signaling effector CTNNB1. WNT4- and CTNNB1-overexpressing cultured granulosa cells were analyzed by microarray for alterations in gene expression, which showed that WNT4 also regulates a series of genes involved in late follicle development and the cellular stress response via the WNT/CTNNB1 signaling pathway. Together, these data indicate that WNT4 is required for normal antral follicle development, and may act by regulating granulosa cell functions including steroidogenesis.
Publication Title
WNT4 is required for normal ovarian follicle development and female fertility.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene-expression profiles by microarrays can be very useful to characterize new potential candidate genes, key regulatory networks, and to define phenotypes or molecular signatures to improve the diagnosis or classification of the disease. We have used this approach in the study of one of the major causes of allergic diseases in Mediterranean countries, the olive pollen response, in order to find differential molecular markers among five clinical groups, Non-allergic, Asymptomatic, Allergic but not to olive pollen, Non-treated, olive pollen allergic patients and Olive pollen allergic patients (under specific-immunotherapy). The results of gene-expression by principal components analysis (PCA) clearly showed five clusters of samples that correlated with the five clinical groups. Analysis of differential gene-expression by multiple testing, and functional analysis by KEGG and Gene-Ontology revealed differential genes and pathways among the 5 clinical groups.
Publication Title
Differential gene-expression analysis defines a molecular pattern related to olive pollen allergy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of gene-expression profiles with microarrays can be very useful to dissect specific responses and to characterize with a global view, new elements for improving the diagnosis, treatment and understanding of allergic diseases. We have used this approach for studying the olive pollen response, taking advantage our previous results of T-cell epitope mapping on Ole e 1 molecule (the major allergen from olive pollen) in order to analyze the stimuli influence on the gene-expression of olive pollen allergic patients. Peripheral blood mononuclear cells (PBMCs) from 6 healthy controls and 6 allergic subjects were stimulated 24 hours with olive pollen stimuli: Ole e 1 molecule and two Ole e 1 peptides previously defined as P2+3 (aa10-31), mainly recognized by non-allergic subjects (possible immunoregulatory epitope) and P10+12+13 (aa90-130), immunodominant T-cell epitope. RNA extracted from basal and stimulated PBMCs was analyzed by HuGeU133 plus 2.0 GeneChip, Affymetrix (38.500genes). After assessment of data quality by standard quality checks and principal components analysis (PCA), differential gene-expression by experimental conditions was performed by multiple testing, using microarrays specific software. Differences in functional analysis were performed by KEGG, for pathways and Gene-Ontology for biological process. The results of gene-expression by PCA showed differential clusters that correlated with the experimental conditions from samples of allergic patients. Analysis of differential gene-expression by multiple testing, and functional analysis by KEGG and Gene-Ontology revealed differential genes and pathways among the 4 experimental conditions.
Publication Title
Therapeutic targets for olive pollen allergy defined by gene markers modulated by Ole e 1-derived peptides.
Sample Metadata Fields
Specimen part, Disease
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