Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA121703 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Branching from conduits is a defining feature of the gas delivery systems of invertebrates (tracheae built from epithelial cells) and vertebrates (vasculature lined by endothelial cells). Here, we show that the vertebrate transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for sprouting of primary human endothelial cells and for the normal development of the Danio rerio embryo blood circulatory system. Tel controls endothelial sprouting via binding to the generic co-repressor C-terminal binding protein (CtBP). In endothelial cells, the Tel:CtBP complex temporally restricts a VEGF-mediated pulse of dll4 expression and consequently integrates VEGFR intracellular signaling and intercellular Notch-Dll4 signaling. It further refines branching by regulating expression of other factors that constrain angiogenesis such as sprouty family members and ve-cadherin. Thus, the Tel:CtBP complex moderates the balance between positive and antagonistic angiogenesis cues and thereby conditions endothelial cells for angiogenesis. Since the activity of CtBP is attuned to intracellular NADH levels, our results raise the possibility that Tel-mediated sprouting could be sensitized to the metabolic status of the tissue. Tel control of branching appears to be evolutionarily conserved since Yan, the invertebrate orthologue of Tel, is similarly required for branching morphogenesis of the invertebrate tracheae. Collectively, our work suggests that Tel is a central regulator of angiogenesis and highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis.
2010-09-09 | GSE19335 | GEO
Project description:Branching from conduits is a defining feature of the gas delivery systems of invertebrates (tracheae built from epithelial cells) and vertebrates (vasculature lined by endothelial cells). Here, we show that the vertebrate transcriptional repressor Tel plays an evolutionarily conserved role in angiogenesis: it is indispensable for sprouting of primary human endothelial cells and for the normal development of the Danio rerio embryo blood circulatory system. Tel controls endothelial sprouting via binding to the generic co-repressor C-terminal binding protein (CtBP). In endothelial cells, the Tel:CtBP complex temporally restricts a VEGF-mediated pulse of dll4 expression and consequently integrates VEGFR intracellular signaling and intercellular Notch-Dll4 signaling. It further refines branching by regulating expression of other factors that constrain angiogenesis such as sprouty family members and ve-cadherin. Thus, the Tel:CtBP complex moderates the balance between positive and antagonistic angiogenesis cues and thereby conditions endothelial cells for angiogenesis. Since the activity of CtBP is attuned to intracellular NADH levels, our results raise the possibility that Tel-mediated sprouting could be sensitized to the metabolic status of the tissue. Tel control of branching appears to be evolutionarily conserved since Yan, the invertebrate orthologue of Tel, is similarly required for branching morphogenesis of the invertebrate tracheae. Collectively, our work suggests that Tel is a central regulator of angiogenesis and highlights Tel and its associated networks as potential targets for the development of therapeutic strategies to inhibit pathological angiogenesis. 2 independent screens were performed testing effects of knockdown of Tel or CtBP (screen 1) or effects of VEGF-A (screen 2) on Human Umbilical Vein Endothelial Cells (HUVECs). For screen 1 we tested 3 different conditions. We established stable HUVEC cell lines which were either infected with control lentivirus (Mock), or lentivirus expressing short hairpin RNA constructs for the specific knockdown of Tel(Teli) or CtBP2 (CtBP2i). Expression in the Teli and CtBP2i cell lines was compared to expression in the Mock cell line for screen 1. For screen 2 we tested 2 conditions. We exposed HUVECs to VEGF (50ng/mL) for 30 minutes (samplename: VEGF30) and compared the transcriptome of these cells to untreated HUVECs (VEGF0). For each condition 2 independent repeats were analyzed and expression of genes was averaged for each repeat. HUVECs were grown under standard conditions (37degrees Celsius, 5% CO2) in EGM2 medium (Lonza).
2010-09-09 | E-GEOD-19335 | biostudies-arrayexpress
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)
2012-06-01 | E-GEOD-38396 | biostudies-arrayexpress
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description: Not available
| S-EPMC4686780 | biostudies-literature
Project description: Not available
| S-EPMC3743458 | biostudies-literature
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.
2010-09-25 | GSE24338 | GEO
Project description: Not available
| S-EPMC5738339 | biostudies-literature
Project description: Not available
| S-EPMC5935238 | biostudies-literature