Project description:This SuperSeries is composed of the following subset Series: GSE12011: Regulation of human endothelial gene expression by miR-126 GSE12012: Regulation of zebrafish endothelial gene expression by miR-126 Refer to individual Series
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:The goal of this study is to investigate the cell type-specific targets of miR-126-3p in human lung microvascular endothelial cells (HLMVEC). Following the transfections of HLMVEC with non-targeting negative controls, miR-126 mimics, or miR-126 antisense inhibitors, we calculated the copy number concentration of miR-126 in each sample and performed genome-wide RNA sequencing. Plotting the gene expression data for each transfection condition (Scramble, 126-OE and 126-KD) against their respective miR-126 concentrations, we performed a linear regression analysis to discover genes that were the most sensitive to changes in miR-126 levels. We identified 1258 genes that were upregulated and 1436 genes that were downregulated by miR-126-3p. Further comparison between the downregulated genes in HLMVEC and targets predicted by online databases including TargetScan and miRDB revealed 6 genes as potential direct targets of miR-126-3p. Our study is the first to report targets of miR-126-3p in HLMVEC and demonstrate the effect of miR-126 level alteration on the HLMVEC global transcriptome. These results add to the diverse functions of miR-126-3p in different endothelial cell types and provide basis for the development of cell type-specific treatment for lung diseases.
Project description:Retinal neovascularization is a severe complication of several neovascular retinal diseases, including proliferative diabetic retinopathy, central retinal vein occlusion and retinopathy of prematurity. MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. Here, we investigate the retinal miRNA expression profile in a rat model of oxygen-induced retinopathy (OIR) using miRNA-Seq. We show that miR-143-3p, miR-126-3p, and miR-150-5p are significantly downregulated in the retina of OIR rats, and intravitreal injection of synthetic mimics of these miRNAs significantly ameliorate retinal neovascularization in this animal model. Of these identified miRNAs, miR-143 which is highly expressed in the neural retina and retinal vasculature is here identified for the first time to be associated with retinal neovascularization. With a focus on miR-143 expression in primary human retinal endothelial cells, we explore its involved pathways through a multi-omics analysis. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodelling. Consequently, the multi-omics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating HIF signalling pathway. Furthermore, using cytoHubba, a topological analysis method to assess the essentiality of genes, we predict 20 top hub genes regulated by miR-143 that may be involved in mediating endothelial cell function. Using CIBERSORTx, a bulk gene expression deconvolution algorithm, we analyze a public RNA-Seq dataset (GSE102485) and demonstrate that the retinal neovascular membranes in patients with proliferative diabetic retinopathy (PDR) principally consist of endothelial cells. We then identify 2 hub genes, THBS1 and SERPINE1, direct targets of miR-143, which on further analysis demonstrate an expression level significantly altered in the PDR patients compared to controls. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization. The present study might have important implications for the exploration of potential therapeutic targets for the treatment of neovascular ocular diseases.
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6