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Hypoxia & Cell Fate

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Oxygen sensing in cardiovascular progenitors cell fate decisions

Cardiogenesis is a complex process that involves different cell types that have to mature to form the final functional heart compartments. Isl1 cardiovascular progenitors label the second heart field and contribute to myocardial,... ver más

28/02/2015

CENTRO NACIONAL DE...

100K€

Presupuesto del proyecto: 100K€

Líder del proyecto

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASC... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 28M€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2015-02-28 No tenemos la información de la convocatoria

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Líder del proyecto

CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASC... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5 | 28M€

Presupuesto del proyecto 100K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cardiogenesis is a complex process that involves different cell types that have to mature to form the final functional heart compartments. Isl1 cardiovascular progenitors label the second heart field and contribute to myocardial, smooth muscle and endothelial structures of the heart. These progenitors have been extensively studied but little is know about the extracellular signals mediating their cell fate decisions and biology. A more recent group of cardiovascular progenitors arising from the epicardium and labeled by the expression of Tbx18 or Wt1 have been reported to contribute to the coronary arterial tree, cardiac fibroblasts and atrial and ventricular cardiomyocytes. Embryonic hypoxia has been involved in cardiovascular system development, while the molecular mechanisms controlling the adaptation to low oxygen tensions during heart formation remain poorly understood. Thus, I aim to determine if changes in the oxygen supply could regulate early cardiovascular progenitor’s proliferation, migration or commitment towards specific differentiated cardiac lineages and evaluate the concept of hypoxia as a potential niche for cardiovascular progenitors. We aim to study cellular properties and mechanisms that might be influenced by hypoxia as cell metabolism, transcriptional regulation and modulation of morphogenic signaling pathways. Several reporter embryonic stem cell lines will be used as in vitro systems to trace and isolate discrete pools of cardiovascular progenitors after exposure to different oxygen tensions and recapitulate cardiac development in a dish. Additionally in vivo mouse models of conditional deletion of hypoxia pathway elements (HIFs, VHL, PHDs) in cardiovascular progenitors will be employed to confirm the in vitro data and to determine of the role of hypoxia in early cardiogenesis. Unraveling these points could open a research avenue towards new methodologies in the cardiovascular stem cell field and may have therapeutic significance.

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