Objetivo
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.
Ámbito científico
Convocatoria de propuestas
ERC-2012-ADG_20120314
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Régimen de financiación
ERC-AG - ERC Advanced GrantInstitución de acogida
91904 Jerusalem
Israel