Objetivo Angiogenesis research has focused on the sprouting of new capillaries. The mechanisms of vessel maturation are much less well understood. Yet, the maintenance of a mature, quiescent, and organotypically-differentiated layer of endothelial cells (ECs) lining the inside of all blood vessels is vital for human health. The goal of ANGIOMATURE is to identify, validate, and implement novel mechanisms of vascular maturation and organotypic EC differentiation that are active during development, maintenance of vascular stability in adults, and undergo changes in aging. We recently identified previously unrecognized gene expression signatures of vascular maturation in a genome-wide screen of ECs isolated from newborn and adult mice. Epigenetic mechanisms were identified that control the EC transcriptome through gain and loss of DNA methylation as well as EC differentiation and signaling specification. These findings pave the way for groundbreaking novel opportunities to study vascular maturation. By characterizing functionally diverse types of blood vessels, including continuous ECs in lung and brain and sinusoidal ECs in liver and bone marrow, the ANGIOMATURE project will (1) determine up to single cell resolution the transcriptional and epigenetic program(s) of vascular maturation and organotypic differentiation during adolescence, (2) analyze the functional consequences of such program(s) in differentiated ECs and their adaptation to challenge, and (3) study changes of maturation and differentiation program(s) and vascular responses during aging. We will towards this end employ an interdisciplinary matrix of approaches involving omics, systems biology, conditional gene targeting, organoid cell culture, and experimental pathology to create a high-resolution structural and functional organotypic angioarchitectural map. The project will thereby yield transformative mechanistic insights into vital biological processes that are most important for human health and healthy aging. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesbasic medicinepathologymedical and health sciencesbasic medicinephysiologyhomeostasisnatural sciencesbiological sciencesgeneticsepigenetics Palabras clave Vascular Biology Endothelial Cell Biology Vascular Differentiation Organotypic Vasculature Epigenetic regulation Programa(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Tema(s) ERC-2017-ADG - ERC Advanced Grant Convocatoria de propuestas ERC-2017-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-ADG - Advanced Grant Institución de acogida RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG Aportación neta de la UEn € 1 275 000,00 Dirección SEMINARSTRASSE 2 69117 Heidelberg Alemania Ver en el mapa Región Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 275 000,00 Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación neta de la UE Ampliar todo Contraer todo RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG Alemania Aportación neta de la UEn € 1 275 000,00 Dirección SEMINARSTRASSE 2 69117 Heidelberg Ver en el mapa Región Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo de actividad Higher or Secondary Education Establishments Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 275 000,00 DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Alemania Aportación neta de la UEn € 1 063 918,00 Dirección IM NEUENHEIMER FELD 280 69120 Heidelberg Ver en el mapa Región Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo de actividad Research Organisations Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 1 063 918,00
