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GSE55607
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mutations of STAT3 underlie the autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). STAT3 has critical roles in immune cells and thus, hematopoietic stem cell transplantation (HSCT), might be a reasonable therapeutic strategy in this disease. However, STAT3 also has critical functions in non-hematopoietic cells and dissecting the protean roles of STAT3 is limited by the lethality associated with germline deletion of Stat3. Thus, predicting the efficacy of HSCT for HIES is difficult. To begin to dissect the importance of STAT3 in hematopoietic and non-hematopoietic cells as it relates to HIES, we generated a mouse model of this disease. We found that these transgenic mice recapitulate multiple aspects of HIES, including elevated serum IgE and failure to generate Th17 cells. We found that these mice were susceptible to bacterial infection that was partially corrected by HSCT using wild type bone marrow, emphasizing the role played by the epithelium in the pathophysiology of HIES.
Publication Title
A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The role of FoxP3+ regulatory T (Treg) cells in the maintenance of immunological tolerance is well established. Recently, genome-wide association studies (GWAS) in humans have associated polymorphisms within the BACH2 locus encoding the transcription factor BTB and CNC homology 1, basic leucine zipper transcription factor 2 (Bach2) with diverse allergic and autoimmune diseases including asthma, multiple sclerosis, Crohn's disease, celiac disease, generalized vitiligo and type 1 diabetes. Common to these diseases is a failure to adequately maintain immunological tolerance. However, a role for Bach2 in this process has not been established.Here, by assessing the phenotype of mice in which the Bach2 gene is disrupted, we demonstrate a non-redundant role for Bach2 in the prevention of a spontaneous lethal inflammatory disorder predominantly affecting the lung and gut with excessive T helper 2 (Th2) responses and formation of circulating autoantibodies. Bach2 was necessary for efficient induction of FoxP3 expression both during thymopoesis and upon stimulation of nave peripheral CD4+ T cells under Treg polarizing conditions in vitro. Consequently, in bone marrow reconstitution experiments, Bach2 expression within the haematopoetic system was necessary for suppression of lethal autoimmunity in a manner that was FoxP3 dependent. These findings demonstrate a requirement for Bach2 in early lineage commitment of both thymic and induced Treg cells and point to shared mechanisms that underlie diverse allergic and autoimmune disorders that may serve as targets in the development of novel therapeutic strategies.
Publication Title
BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 96 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Carbonyl chloride (phosgene) is a toxic industrial compound (TIC) widely used in industry for the production of synthetic products, such as polyfoam rubber, plastics, and dyes. Exposure to phosgene results in a latent (1-24 hr), potentially life-threatening pulmonary edema and irreversible acute lung injury. A genomic approach was utilized to investigate the molecular mechanism of phosgene-induced lung injury. CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m3 (8 ppm) phosgene for 20 min (640 mg x min/m3). Lung tissue was collected from air- or phosgene-exposed mice at 0.5, 1, 4, 8, 12, 24, 48, and 72 hr post-exposure. RNA was extracted from the lung and used as starting material for the probing of oligonucleotide microarrays to determine changes in gene expression following phosgene exposure. The data were analyzed using principal component analysis (PCA) to determine the greatest sources of data variability. A three-way analysis of variance (ANOVA) based on exposure, time, and sample was performed to identify the genes most significantly changed as a result of phosgene exposure. These genes were rank ordered by p-values and categorized based on molecular function and biological process. Some of the most significant changes in gene expression reflect changes in glutathione synthesis and redox regulation of the cell, including upregulation of glutathione S-transferase alpha-2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit (also known as -glutamyl cysteine synthetase). This is in agreement with previous observations describing changes in redox enzyme activity after phosgene exposure. We are also investigating other pathways that are responsive to phosgene exposure to identify mechanisms of toxicity and potential therapeutic targets.
Publication Title
Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 27 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Sulfur mustard (HD) is a vesicating agent that targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function.
Publication Title
Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 187 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The tissue of origin form metastatic tumors is sometimes difficult to identify from clinical and histologic information. Gene expression signatures are one potential method for identifying the tissue of origin. In the development of algorithms to identify tissue of origin, a collection of human tumor metastatic specimens with known primary sites or primary tumors with poor differentiation are very useful in identifying gene expressions signatures that can classify unknown specimens as to the tissue of origin. Here we describe a series of 276 such tumor specimens used for this purpose. The specimens are poorly differentiated, undifferentiated and metastatic specimens from tumors of the following types/tissues of origin: breast, liver, non-Hodgkin's lymphoma, non-small cell lung cancer, ovary, testicular germ cell, thyroid, kidney, pancreas, colorectal cancer, soft tissue sarcoma, bladder, gastric cancer, prostate and melanoma. This data combined with other series (GSE2109) was used to validate a proprietary tumor classification algorithm of Pathwork Diagnostics. The results of this validation set (N = 545 CEL files) showed that the algorithm correctly identified the tissue of origin for 89.4% of the specimens.
Publication Title
Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin.
Sample Metadata Fields
Sex, Age
View Samples- Rattus norvegicus
- 153 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Male Sprague-dawley rats were exposed to saline, isopropyl alcohol, 1mg/kg, 3mg/kg or 6 mg/kg sulfur mustard for 30 min, 1 hr, 3 hr, 6 hr, or 24 hr before analysis of lung tissue by oligonucleotide array analysis.
Publication Title
Genomic analysis of rodent pulmonary tissue following bis-(2-chloroethyl) sulfide exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cellular responses to carcinogens are typically studied in transformed cell lines, which do not reflect the physiological status of normal tissues. To address this question, we have characterized the transcriptional program and cellular responses of normal human lung WI-38 fibroblasts upon exposure to the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE). Exposure to BPDE induces a strong inflammatory response in WI-38 primary fibroblasts. Whole-genome microarray analysis shows induction of several genes related to the production of inflammatory factors, including those that encode interleukins (ILs), growth factors, and enzymes related to prostaglandin synthesis and signaling. This is the first demonstration that a strong inflammatory response is triggered in primary fibroblasts in response to a reactive diol epoxide derived from a polycyclic aromatic hydrocarbon.
Publication Title
Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We explored the transcriptional modification induced by CD99 transfection in the osteosarcoma cell lines SaOS-2 after 0, 7 and 14 days in differentiation medium.
Publication Title
Integrated approaches to miRNAs target definition: time-series analysis in an osteosarcoma differentiative model.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IRF-8 extinguishes neutrophil production and promotes dendritic cell lineage commitment in both myeloid and lymphoid mouse progenitors.
Sample Metadata Fields
Specimen part
View Samples