This SuperSeries is composed of the SubSeries listed below.
Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.
Sex, Specimen part, Disease, Disease stage
View SamplesGlobal gene expression analysis of inflammatory leiomyosarcoma (ILMS) and conventional leiomyosarcoma (LMS).
Retained heterodisomy is associated with high gene expression in hyperhaploid inflammatory leiomyosarcoma.
Specimen part, Disease, Disease stage
View SamplesA biobank collection of carotid plaque samples taken from patients undergoing endarterectomy operations.
Prediction of ischemic events on the basis of transcriptomic and genomic profiling in patients undergoing carotid endarterectomy.
Specimen part, Disease, Subject
View SamplesThe aim of this study was to investigate if milk fat globule membrane (MFGM) enclosing the dairy fat influence peripheral blood mononuclear cells (PBMC) gene expression. This study was a 8-week single-blind, randomized, controlled isocaloric trial with two parallel groups including overweight (mean BMI: 28) adult women (n=30). All subjects consumed 40 g dairy fat per day either as cream (MFGM diet) or as butter oil (control diet).
Potential role of milk fat globule membrane in modulating plasma lipoproteins, gene expression, and cholesterol metabolism in humans: a randomized study.
Age, Specimen part, Time
View SamplesFull title: Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication
Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication.
Specimen part
View SamplesRationale - Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage specification factor FOXP3 is essential for Treg cells' ability to uphold immunological tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective - To define the regulation and functions of the two major FOXP3 isoforms, FOXP3fl and FOXP3?2, as well as to establish whether their expression is associated with ischemic atherosclerotic disease. Methods and Results - Human primary T-cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3?2. FOXP3?2 induced specific transcription of GARP, which functions by tethering the immunosuppressive cytokine TGF-ß to the cell membrane of activated Treg cells. RT-PCR was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of over 150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3?2 transcript usage, when comparing plaques from patients without symptoms and patients with occurrence of recent (<1 month) vascular symptoms including minor stoke, transient ischemic attack or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these two groups. Conclusions - These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3?2 controls a transcriptional program that acts protectively in human atherosclerotic plaques. Overall design: In this experiment we have analyzed 3 groups of each 3 biological repliactes equalling 9 samples in total.
Alternative Splicing of <i>FOXP3</i> Controls Regulatory T Cell Effector Functions and Is Associated With Human Atherosclerotic Plaque Stability.
Subject
View SamplesDeficiencies in the ATM gene are the underlying cause for ataxia telangiectasia, a congenital syndrome characterized by neurological, motor and immunological defects, as well as a predisposition to cancer risks. MicroRNAs (miRNAs) are small regulators of post-transcriptional gene expression and a useful tool for cancer diagnosis, staging, and prediction of therapeutic responses to clinical regimens. In particular, miRNAs have been used to develop signatures for breast cancer profiling. We are interested in the consequences of ATM deficiency on miRNA expression in breast epithelial cells and the potential contribution to cancer predisposition. In this study we investigate the effects of ATM loss on the miRNA expression and related gene expression changes in normal human mammary epithelial cells (HME-CC). We have identified 81 significantly differently expressed miRNAs in the ATM-deficient HME-CCs using small RNA sequencing. Many of these differentially expressed miRNAs have been described and implicated in tumorigenesis and proliferation. These changes include down-regulation of tumor suppressor miRNAs, such as hsa-miR-29c and hsa-miR-16, as well as the over-expression of pro-oncogenic miRNAs hsa-miR-93 and hsa-mir-221. All 81 miRNAs were combined with genome wide gene expression profiles to investigate possible targets of miRNA regulation. We identified messenger RNA (mRNA) targets of these miRNAs that were also significantly regulated after the depletion of ATM. Predicted targets included many genes implicated in cancer formation and progression, including SOCS1 and the proto-oncogene MAF. Integrated analysis of miRNA and mRNA expression allows us to build a more complete understanding of the pathways and networks involved in the breast cancer predisposition observed in individuals deficient in ATM. This study highlights miRNA and predicted mRNA target expression changes in ATM-deficient HME-CCs and suggests a mechanism for the breast cancer-prone phenotype seen in ATM deficient cells and patients. Additionally, this study provides preliminary data for defining miRNA profiles that may be used prognostic biomarkers for breast cancer predisposition. Overall design: Examination of small RNA population in human mammary epithelial cell lines. Each condition was preformed in triplicate.
Genome-wide small RNA sequencing and gene expression analysis reveals a microRNA profile of cancer susceptibility in ATM-deficient human mammary epithelial cells.
Specimen part, Cell line, Subject
View SamplesThe objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells. The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined. In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle. We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks. This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Specimen part
View SamplesThe objective is to identify genes that are differentially expressed following the introduction of DNA double-strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired, and thus, will provide a continuous stimulus to the cell.
DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs.
Specimen part, Disease, Treatment
View SamplesThe use of calcineurin inhibitor (CI) immunosuppressants has significantly improved the early allograft survival rate in organ transplantation. However, CI therapy has been associated with chronic nephrotoxicity, which limits their long-term utility. In order to understand the mechanisms of the toxicity, we analyzed the gene expression changes that underlie the development of CI immunosuppressant-mediated nephrotoxicity, in male Sprague-Dawley (SD) rats dosed daily with cyclosporine (CsA), FK506 or rapamycin (Rapa) for 1 to 28 days. We identified a group of genes, whose expression in rat kidney is quantitatively correlated with CI-induced kidney injury as observed in changes in blood urea nitrogen (BUN) levels and kidney histopathology. These genes include both up-regulated genes, such as Ren1 and Klks3, and down-regulated genes, such as Calb1, Egf, NCC, and kidney specific Wnk1 (KS-Wnk1). Using the down-regulated genes alone we successfully predicted CI immunosuppressant-mediated kidney injury in rats following 7 days of treatment. Among these genes are two mechanism-related genes, NCC and KS-Wnk1, both of which are involved in the sodium transport in the distal nephrons. The down-regulation of both genes at the mRNA and protein level in rat kidney following CI treatment was confirmed by quantitative RT-PCR and immunohistochemical staining, respectively. We hypothesize that decreased expression of NCC may cause reduced sodium chloride reabsorption in the distal tubules, and contribute to the prolonged activation of the Renin-Angiotensin-System (RAS), a demonstrated contributor to the development of CI-induced nephrotoxicity in both animal models and clinical settings. Therefore, NCC and KS-Wnk1 could potentially be used as biomarkers for early detection and prevention of CI-related nephrotoxicity in clinical practice.
Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity.
Sex, Specimen part
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