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GSE10870
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Ablation of the Srf gene in dopaminoceptive neurons of the brain was performed using the Cre/loxP system, with the recombinase expressed from a BAC-derived Drd1a promoter.
Publication Title
Loss of the serum response factor in the dopamine system leads to hyperactivity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
STEAP4 is a plasma membrane metallo-reductase involved in the transport of iron and copper. Recently, STEAP4 was implicated in promoting insulin sensitivity by acting in white adipose tissue (WAT) to control the production of inflammatory cytokines such as IL-6. Indeed, the loss of STEAP4 expression in mice leads to increased production of inflammatory cytokines in visceral WAT and systemic insulin resistance. In this report, we demonstrate that in mouse liver STEAP4 is produced at significant levels and that STEAP4 transcription is induced by IL-6. We further demonstrate that the STEAP4 gene is a direct target of phosphorylated STAT3 in mouse liver. In addition, hepatic STEAP4 expression is regulated by feeding and fasting, and obesity leads to the induction of STEAP4 expression in the liver. Interestingly, the regulation of STEAP4 in both feeding and fasting and the obese state appears to require the transcription factor C/EBPalpha that may act in concert with STAT3 as they both bind to the proximal STEAP4 promoter in vivo. Taken together these data suggest the transcriptional regulation of hepatic STEAP4 may play a critical role in the response to nutritional and inflammatory stress and contribute to the protective effect of STEAP4 in vivo.
Publication Title
Regulation of hepatic six transmembrane epithelial antigen of prostate 4 (STEAP4) expression by STAT3 and CCAAT/enhancer-binding protein alpha.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The transcription factor MEF2C is specifically induced by VEGF in endothelial cells. To delineate target genes of MEF2C in endothelial cells, which might be important during angiogenesis also, MEF2C was overexpressed adenovirally in human umbilical vein endothelial cells (HUVECs) over a period of 8 to 32 hours.
Publication Title
The transcription factor MEF2C negatively controls angiogenic sprouting of endothelial cells depending on oxygen.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
NCoR1 (Nuclear receptor Co-Repressor) and SMRT (Silencing Mediator of Retinoid and Thyroid hormone receptor) are well-recognized coregulators of nuclear receptor (NR) action. However, their unique roles in the regulation of thyroid hormone (TH) signaling in specific cell types have not been determined. To accomplish this we generated a mouse model that lacked function of either NCoR1 or SMRT or both in the liver only. Despite both corepressors being present in the liver, SMRT had no ability to regulate TH signaling when deleted in either euthyroid or hypothyroid animals. In contrast, disruption of NCoR1 action confirmed that it is the principal mediator of TH sensitivity in vivo. While SMRT played little role in TH signaling alone, when disrupted in combination with NCoR1 it greatly accentuated the activation of hepatic lipogenesis regulated by NCoR1. Thus, corepressor specificity exists in vivo and NCoR1 is the principal regulator of TH action in the liver. However, both NCoR1 and SMRT collaborate to control hepatic lipogenesis and lipid storage, which likely reflects their cooperative activity in regulating the action of multiple NRs including the thyroid hormone receptor (TR).
Publication Title
NCoR1 and SMRT play unique roles in thyroid hormone action in vivo.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The thyroid hormone receptor (TR) has been proposed to regulate target genes in the absence of triiodothyronine (T3), through the recruitment of the corepressors, NCoR and SMRT. NCoR and SMRT may thus play a key role in both hypothyroidism and resistance to thyroid hormone, though this has never been tested in vivo. To accomplish this we developed mice that express in the liver a NCoR protein (L-NCoRID) that cannot interact with the TR. L-NCoRID mice develop normally, however when made hypothyroid the repression of many positively regulated T3-target genes is abrogated, demonstrating that NCoR plays a specific and sufficient role in repression by the unliganded TR. Remarkably, in the euthyroid state, expression of many T3-targets are also upregulated in L-NCoRID mice, demonstrating that NCoR also determines the magnitude of the response to T3 in euthyroid animals. While positive T3 targets were upregulated in L-NCoRID mice in the hypo and euthyroid state there was less effect seen on negatively regulated T3 target genes. Thus, NCoR is a specific regulator of T3-action in vivo and mediates the activity of the unliganded TR. Furthermore, NCoR may play a key role in determining the differences in individual responses to similar levels of circulating T3.
Publication Title
The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as operationally tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter fingerprint of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.
Publication Title
Multiparameter immune profiling of operational tolerance in liver transplantation.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 122 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Large scale transcriptome analysis of Wistar and Sprague Dawley rat tissues.
Publication Title
Applications of a rat multiple tissue gene expression data set.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Adipose tissue inflammation and atherosclerosis are the main mechanisms behind type 2 diabetes and cardiovascular disease respectively, the major risks associated with the metabolic syndrome. Studies considering more than single factors behind the complexity of the metabolic syndrome are valuable to achieve a better and wider understanding of the metabolic syndrome. In this study common dysregulated pathways between adipose tissue inflammation and atherosclerosis were identified using two different bioinformatic tools to perform pathway analysis. First, we run a gene set enrichment analysis utilizing with data from two microarray experiments done with gonadal white adipose tissue and atherosclerotic aorta. Once the common dysregulated pathways between both tissues were identify, the inflammatory response and the oxidative phosphorylation pathways from the Hallmark geneset were selected to conduct a deeper checkup at the single gene level of these pathways. Second, we carried out a pathway analysis validation with the Panther software combining the microarray data with a published type 2 diabetes mellitus metanalysis and cardiovascular disease metanalysis which included human data. In conclusion, this study provides worthwhile data pointing out and describing several dysregulated and common pathways in adipose tissue inflammation and atherosclerotic aorta with a potential implication in the pathogenesis of type 2 diabetes and atherosclerosis.
Publication Title
Common dysregulated pathways in obese adipose tissue and atherosclerosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We aimed at identifying lymphangiogenic subpopulations by comparative analysis of single cell clones derived from a melanoma of a single patient. Selected clones were grafted into SCID mice, where they induced lymphangiogenesis and metastasized into sentinel nodes, whereas non-lymphangiogenic clones from the same patient did not metastasize. RNA isolated from primary SCID mouse tumors were used for transcriptome analysis.
Publication Title
MET expression in melanoma correlates with a lymphangiogenic phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Endothelial cells comprise a key component of the inflammatory response. HUVEC (human umbilical vein endothelial cells) were stimulated with interleukin-1 for 0, 0.5, 1, 2.5 and 6 hours, and analyzed using Affymetrix U133A microarrays, in order to obtain a comprehensive overview of the immediate early to early gene expression profiles. HUVEC were isolated and cultured on gelatine-coated cell culture dishes in M199 medium supplemented with 20% FCS, antibiotics, ECGS (endothelial cell growth supplement) and Heparin as described by Zhang et al., Blood 1996;88:3880-3886. HUVEC were stimulated with 100 U/ml human IL-1 (Biosource) for various periods of time, and total RNA isolated using the RNeasy kit (Qiagen) according to the manufacturer's instructions. Hybridization to one set of human U133A GeneChips (Affymetrix, Santa Clara, CA) and scanning of the arrays was carried out according to manufacturers protocols (https://www.affymetrix.com). Briefly, 5 g of total RNA was used to generate double-stranded cDNA by reverse transcription using a cDNA synthesis kit (Superscript Choice System; Life Technologies, Inc., Rockville, MD) that uses an oligo(dT)24 primer containing a T7 RNA polymerase promoter 3' to the polyT (Geneset, La Jolla, CA), followed by second-strand synthesis. Labeled cRNA was prepared from the double-stranded cDNA by in vitro transcription using T7 RNA polymerase in the presence of biotin-11-CTP and biotin-16-UTP (Enzo, Farmington, NY). The labeled cRNA was purified over RNeasy columns (Qiagen, Valencia, CA). Fifteen g of cRNA was fragmented at 94C for 35 minutes in 40 mmol/L of Tris-acetate, pH 8.1, 100 mmol/L of potassium acetate, and 30 mmol/L of magnesium acetate. The cRNA was then used to prepare 300 l of hybridization cocktail (100 mmol/L MES, 1 mol/L NaCl, 20 mmol/L ethylenediaminetetraacetic acid, 0.01% Tween 20) containing 0.1 mg/ml of herring sperm DNA (Promega, Madison, WI) and 500 g/ml of acetylated bovine serum albumin (Life Technologies, Inc.). Before hybridization, the cocktails were heated to 94C for 5 minutes, equilibrated at 45C for 5 minutes, and then clarified by centrifugation (16,000 x g) at room temperature for 5 minutes. Aliquots of this hybridization cocktail containing 15 g of fragmented cRNA were hybridized to HU133A arrays (Affymetrix, Santa Clara, CA) at 45C for 16 hours in a rotisserie oven at 60 rpm. The arrays were washed using non-stringent buffer (6xSSPE: 0.9 M sodium chloride, 0.06 M sodium phosphate, 6 mM EDTA pH 7.4) at 25C, followed by stringent buffer (100 mmol/L MES, pH 6.7, 0.1 mol/L NaCl, 0.01% Tween 20) at 50C. The arrays were stained with streptavidin-phycoerythrin (Molecular Probes, Eugene, OR), washed with 6xSSPE, incubated with biotinylated anti-streptavidin IgG, stained again with streptavidin-phycoerythrin, and washed again with 6xSSPE. The arrays were scanned using the GeneArray scanner (Affymetrix). Image analysis was performed with GeneChip software (Affymetrix, MAS 5.0). Normalization was performed by global scaling, with the arrays scaled to an average intensity of 500.
Publication Title
Deciphering regulatory patterns of inflammatory gene expression from interleukin-1-stimulated human endothelial cells.
Sample Metadata Fields
No sample metadata fields
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