title: Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction.
abstract: Interactions of adult neural stem cells (NSCs) with supportive vasculature appear critical for their maintenance and function, although the molecular details are still under investigation. Neurotrophin (NT)-3 belongs to the NT family of trophic factors, best known for their effects in promoting neuronal survival. Here we show that NT-3 produced and secreted by endothelial cells of brain and choroid plexus capillaries is required for the quiescence and long-term maintenance of NSCs in the mouse subependymal niche. Uptake of NT-3 from irrigating vasculature and cerebrospinal fluid (CSF) induces the rapid phosphorylation of endothelial nitric oxide (NO) synthase present in the NSCs, leading to the production of NO, which subsequently acts as a cytostatic factor. Our results identify a novel interaction between stem cells and vasculature/CSF compartments that is mediated by an unprecedented role of a neurotrophin and indicate that stem cells can regulate their own quiescence in response to endothelium-secreted molecules.
authors.affiliation: Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain; Departamento de Microbiología y Biología Celular, Universidad de La Laguna, 38204 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Delgado
authors.affiliation: Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Sacri R
authors.initials: SR
authors.lastname: Ferrón
authors.affiliation: Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Vicente
authors.affiliation: Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Porlan
authors.affiliation: Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Perez-Villalba
authors.affiliation: Departamento de Microbiología y Biología Celular, Universidad de La Laguna, 38204 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Trujillo
authors.affiliation: Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: D'Ocón
authors.affiliation: Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain. Electronic address: isabel.farinas@uv.es.
authors.forename: Isabel
authors.initials: I
authors.lastname: Fariñas
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D020933:Neurotrophin 3 / Q000378:metabolism*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism
chemical_list: D020933:Neurotrophin 3; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III