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Content archived on 2024-05-29

Specification of Arterial Venous Identity in Embryonic Stem Cells

Objective

During embryonic development, formation of a functional cardiovascular system is critical for survival. When genes essential for cardiovascular development are ablated, embryos die by mid-gestation. Interestingly, this includes ablation of genes for arterial-venous (AV) differentiation indicating that arteries and veins are specified very early in development and that this specification is essential for proper cardiovascular function. AV identity was originally believed to be a trait acquired through local environmental cues. Recent evidence, however, has put this belief into question since arterial markers are expressed by endothelial cells before the onset of erythroblast circulation.

Though the initial AV identity of endothelial cells may be genetically pre-determined, this identity remains plastic during development such that it can be reversed by altering local flow dynamics. Thus, specification of arterial-venous fate involves a complex interaction between signalling molecules and blood flow dynamics. In order to understand the role of these various inputs, we suggest combining the use of embryonic stem (ES) cell culture with micro-electro mechanical systems (MEMS) to allow us to expose small populations of ES cells to control environmental and chemical cues. Using the MEMS technology, flow and pressure can be controlled in channels equivalent to the size of embryonic vasculature, between 50-100µm.

This technology has previously been used to understand the reaction of individual endothelial cells to environmental cues, however has never been applied to ES cells in order to understand the role of mechanical forces in endothelial cell differentiation. This research will thereby investigate which signals, both mechanical and genetic, are necessary for proper AV differentiation and improve our understanding of this process in vivo.

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-7
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Funding Scheme

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IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
EU contribution
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Address
CHU Henri Mondor, 51 Avenue Marechal de Lattre de Tassigny
CRETEIL CEDEX
France

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Total cost

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