To identify genes with expression levels that are associated with T1D progression from AbP (islet autoantibody positive), global gene expression changes were analyzed in AbP subjects with different T1D progression rate.
Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.
Specimen part
View SamplesA common method used both in vitro and in vivo, to identify Tregs in CD4+ T cells is through the characterization of surface marker CD25. Although CD25 expression is well correlated with regulatory activity in vitro, CD4+CD25+ T cells are not the only regulatory CD4+ T cells in vivo. Studies suggest that in many situations, CD4+CD25 T cells are as effective as CD4+CD25+ T cells in controlling T cell mediated disease. Therefore, CD25 is not a uniquely specific cell surface marker for the identification of Tregs. CD49f is an 6-integrin subunit which dimerizes with either the 1 or 4 subunit to form receptors for various laminin isoforms. We found that CD4+ T cells from NOD mice express CD49f, and old non-diabetic NOD mice had an increase of CD4+CD49f+ T cells in the spleen and peripheral lymph node when compared to both young and diabetic mice.
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Sex, Specimen part
View SamplesDisordered angiogenesis is implicated in the pulmonary vascular remodeling secondary to congenital heart disease (CHD). However, the underlying genes are not well delineated. We have previously shown that an ovine model of CHD with increased pulmonary blood flow (PBF, Shunt) has an angiogenesis burst between 1-4 weeks of age. Thus, we hypothesized that the increased pulmonary blood flow elicited a pro-angiogenic gene expression profile prior to the onset of vessel growth. To test this we utilized microarray analysis to identify genes that could be responsible for the angiogenic response. Total RNA was isolated from the lungs of Shunt and Control lambs at 3 days of age and hybridized to Affymetrix GeneChips for microarray analyses (n=8 for each group). A total of 89 angiogenesis-related genes were found to be up-regulated and 26 angiogenesis-related genes down-regulated in Shunt lungs compared to control (cutting at 1.2 fold difference, P<0.05). We then confirmed the up-regulation of pro-angiogenic genes: FGF2, Angiopoietin2 (Angpt2), and Birc5 at both mRNA and protein levels and the up-regulation of ccl2 at mRNA level in the 3-day shunt lungs. Further, we found that pulmonary arterial endothelial cells (PAEC) isolated from juvenile lambs exhibited increased expression of FGF2, Angpt2, Birc5, and ccl2 as well as enhanced angiogenesis when exposed to elevated shear stress (35 dyn/cm2) compared to cells exposed to more physiological level shear stress (20 dyn/cm2). Finally, we demonstrated that blocking FGF2, Angpt2, or Birc 5 signaling, using neutralizing antibodies, significantly decreased the angiogenic response induced by shear stress. In conclusion, we have identified a pro-angiogenic gene expression profile in a lamb model of CHD with increased PBF that precedes the onset of pulmonary vascular remodeling. Further, our data indicate that FGF2, Angiopoietin2, Birc5, and ccl2 may play important roles in the angiogenic response.
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Age, Specimen part, Treatment
View SamplesThe source of aldosterone in 30 to 40 % of patients with primary hyperaldosteronism (PA) is unilateral aldosterone-producing adenoma (APA). The mechanisms causing elevated aldosterone production in APA are unknown. Herein, we examined expression of G-protein coupled receptors (GPCR) in APA and demonstrate that compared to normal adrenals there is a general elevation of certain GPCR in many APA and/or ectopic expression of GPCR in others. RNA samples from normal adrenals (n = 5), APAs (n = 10), and cortisol-producing adenomas (CPAs) (n=13) were used on 15 genomic expression arrays, each of which included 223 GPCR transcripts presented in at least one out of 15 of the independent microarrays. The array results were confirmed using real-time RT-PCR (qPCR). Four GPCR transcripts exhibited a statistically significant increase that was greater than 3-fold compared to normal adrenals, suggesting a general increase in expression compared to normal adrenal glands. Four GPCR transcripts exhibited a greater than 15-fold increase of expression in one or more of the APA samples compared to normal adrenals. qPCR analysis confirmed array data and found the receptors with the highest fold increase in APA expression to be luteinizing hormone receptor (LH-R), serotonin receptor 4 (HTR4), gonadotropin-releasing hormone receptor (GnRHR), glutamate receptor metabotropic 3 (GRM3), endothelin receptor type B-like protein (GPR37), and ACTH receptor (MC2R). There are also sporadic increased expressions of these genes in the CPAs. Together, these findings suggest a potential role of altered GPCR expression in many cases of PA and provide candidate GPCR for further study.
G-protein-coupled receptors in aldosterone-producing adenomas: a potential cause of hyperaldosteronism.
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View SamplesThe loss of PPAR is found to be associated with the development of pulmonary hypertension (PH). We hypothesize that PPAR inhibition induced gene expression changes may underscore the endothelial dysfunction in the disease process.
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View SamplesCD8+ NKT cells are naturally occurring but rare T cells that express both T cell and natural killer (NK) cell markers. These cells may play key roles in establishing tolerance to self antigens; however, the mechanism of action and the molecular profiles of these cells are poorly characterized due to their extremely low frequencies. We developed a highly efficient in vitro conversion/expansion protocol for such cells and extensively characterized their functional and molecular phenotypes using a variety of genomic and immunological techniques.
The IL-10 and IFN-gamma pathways are essential to the potent immunosuppressive activity of cultured CD8+ NKT-like cells.
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View SamplesGene expression profiles were compared between regulatory T cells (Treg) and Effector CD4+ T cells in healthy B6 mice and sick mice with scurfy mutation.
Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset.
Sex, Specimen part
View SamplesAngiotensin II (Ang-II) regulates adrenal steroid production and gene transcription through several signaling pathways. Changes in gene transcription occur within minutes after Ang-II stimulation, causing an acute increase in aldosterone production and subsequent increase in the overall capacity to produce aldosterone. Our goal was to compare the Ang-II regulation of early gene expression and confirm the upregulation of selected genes using quantitative real-time RT-PCR (qPCR) across three species: human, bovine, and rat.
Angiotensin-II acute regulation of rapid response genes in human, bovine, and rat adrenocortical cells.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
ACTH is a potent regulator of gene expression in human adrenal cells.
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View SamplesWe recently showed that inactivation of the WASF3/WAVE3 gene in breast cancer cells results in loss of cell motility and invasion in vitro and metastasis in vivo. To obtain a better understanding of molecular mechanisms of action of WASF3, we have established the stable WASF3 knockdown MDA-MB-231 cells using shRNA strategy.
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Cell line
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