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Project
An integrated study on macrovascular heterogeneity based on stem/progenitor cells and small animal models.
Background:
Research during the last decennium has revealed an extensive heterogeneity among endothelial cells - the cells that line the inside of blood and lymphatic vessels - at the functional, molecular and structural level. This diversity manifests itself at different levels: firstly, there are remarkable differences between endothelial cells from arteries, veins and lymphatic vessels. Moreover, there are unique characteristics for endothelial cells within different hierarchical levels of each of these major vessel types. In addition, there are also important differences at the microvascular level, where the capillary endothelium has adapted itself to the specific needs of the different tissues. Finally, there is also heterogeneity between endothelial cells from different species. Endothelial heterogeneity is the result of a synergy between cell-extrinsic and -intrinsic cues which give rise to a unique 'blueprint'. The (epi)genetically controlled intrinsic factors are retained after culturing the cells in vitro. The extrinsic characteristics are determined by the micro-environment due to biomechanical and biochemical stimuli and are lost very rapidly upon culturing the cells.
Objectives and methods: This doctoral project is part of a larger research program (IMAGINED;
Integrated Multidisciplinary Approach to Gain Insight intoEndothelial
Diversity) and is focused on the macrovascular aspect of endothelial heterogeneity. Objective 1 consists of expanding the current knowledge concerning molecular endothelial heterogeneity. This will be achieved by composing a gene expression profile of arterial, venous, lymphatic (from initial and collector vessels) endothelial cells derived from 4 different species (humans, mice, rats and zebrafish) thereby paying attention to intrinsic and extrinsic factors. Objective 2 is the generation of specialized endothelial subtypes from stem/progenitor cells. For this purpose, the natural micro-environment in which the endothelial cells reside will be mimicked by using different manipulations. Objective 3 will be the in vivo validation of the gene profiles and specialized cells. The role and specificity of blueprint genes will be checkedby different technologies, including staining with antibodies, morpholino knock-down in zebrafish or Xenopus embryos
and the generation of a transgenic reporter mouse. The differentiated endothelial cells will be tested for their potential to generate new specialized vessels in different animal models where there is a preferential need for the provisionof endothelial sybtypes (e.g. arterial endothelial cells in ischemia orlymphatic endothelial cells in lymphedema).
Research during the last decennium has revealed an extensive heterogeneity among endothelial cells - the cells that line the inside of blood and lymphatic vessels - at the functional, molecular and structural level. This diversity manifests itself at different levels: firstly, there are remarkable differences between endothelial cells from arteries, veins and lymphatic vessels. Moreover, there are unique characteristics for endothelial cells within different hierarchical levels of each of these major vessel types. In addition, there are also important differences at the microvascular level, where the capillary endothelium has adapted itself to the specific needs of the different tissues. Finally, there is also heterogeneity between endothelial cells from different species. Endothelial heterogeneity is the result of a synergy between cell-extrinsic and -intrinsic cues which give rise to a unique 'blueprint'. The (epi)genetically controlled intrinsic factors are retained after culturing the cells in vitro. The extrinsic characteristics are determined by the micro-environment due to biomechanical and biochemical stimuli and are lost very rapidly upon culturing the cells.
Objectives and methods: This doctoral project is part of a larger research program (IMAGINED;
Integrated Multidisciplinary Approach to Gain Insight intoEndothelial
Diversity) and is focused on the macrovascular aspect of endothelial heterogeneity. Objective 1 consists of expanding the current knowledge concerning molecular endothelial heterogeneity. This will be achieved by composing a gene expression profile of arterial, venous, lymphatic (from initial and collector vessels) endothelial cells derived from 4 different species (humans, mice, rats and zebrafish) thereby paying attention to intrinsic and extrinsic factors. Objective 2 is the generation of specialized endothelial subtypes from stem/progenitor cells. For this purpose, the natural micro-environment in which the endothelial cells reside will be mimicked by using different manipulations. Objective 3 will be the in vivo validation of the gene profiles and specialized cells. The role and specificity of blueprint genes will be checkedby different technologies, including staining with antibodies, morpholino knock-down in zebrafish or Xenopus embryos
and the generation of a transgenic reporter mouse. The differentiated endothelial cells will be tested for their potential to generate new specialized vessels in different animal models where there is a preferential need for the provisionof endothelial sybtypes (e.g. arterial endothelial cells in ischemia orlymphatic endothelial cells in lymphedema).
Date:1 Oct 2008 → 27 May 2013
Keywords:Macrovascular heterogeneity, stem/progenitor cells
Disciplines:Cardiac and vascular medicine
Project type:PhD project