Objectif Recent evidence suggests that VEGF and the vasculature play multiple roles in organ homeostasis, functions extending far beyond their traditional roles in tissue perfusion. The proposed study represents a vascular-centred approach to the neurovascular unit thriving to gain further insights on the many ways by which blood vessels may affect proper brain functioning. Major focus is on the vascular stem cell niche, i.e. the contention that blood vessels are a key component of adult stem cell niches, including a niche securing proper function of neuronal stem cells (NSCs). Further insights on the niche are also critical for contemplated implementation of stem-cell based therapy. In this multidisciplinary study combining the fields of vascular biology, neurobiology, stem cell biology, and aging research, we harness unique transgenic methodologies to conditionally manipulate (via VEGF) the vasculature within the stem cell niches. We provide a first compelling proof that blood vessels at the niche indeed control stem cells properties and behaviour, evidenced by showing that mere expansion of the niche vasculature and independently of VEGF) increases dramatically adult hippocampal neurogenesis, a process known to be associated with improved cognitive performance. We will determine what aspects of stem cell biology are controlled by juxtaposed, directly contacting blood vessels and will identify signalling systems mediating the vascular/stem cell cross-talk.Adult neurogenesis is known to rapidly decline with age and ways to sustain the process are highly desired. We hypothesize and, in fact, provide initial evidence that expanding and 'rejuvenating' the niche vasculature can override the natural age-dependent decline of adult neurogenesis. Proposed experiments will extend this exciting finding and thrive to uncover the underlying mechanisms. Champ scientifique natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencescell biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil THE HEBREW UNIVERSITY OF JERUSALEM Contribution de l’UE € 2 499 980,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israël Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Hani Ben-Yehuda (Ms.) Chercheur principal Eliahu Keshet (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE HEBREW UNIVERSITY OF JERUSALEM Israël Contribution de l’UE € 2 499 980,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Voir sur la carte Type d’activité Higher or Secondary Education Establishments Contact administratif Hani Ben-Yehuda (Ms.) Chercheur principal Eliahu Keshet (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
