Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction

被引:146
作者
Delgado, Ana C. [1 ,2 ,3 ]
Ferron, Sacri R. [2 ]
Vicente, Diana [4 ]
Porlan, Eva [1 ,2 ]
Perez-Villalba, Ana [1 ,2 ]
Trujillo, Carmen M. [3 ]
D'Ocon, Pilar [4 ]
Farinas, Isabel [1 ,2 ]
机构
[1] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28031, Spain
[2] Univ Valencia, Dept Biol Celular, Valencia 46010, Spain
[3] Univ La Laguna, Dept Microbiol & Biol Celular, San Cristobal De Laguna 38204, Santa Cruz De T, Spain
[4] Univ Valencia, Dept Farmacol, Valencia 46010, Spain
关键词
MICE LACKING; SUBVENTRICULAR ZONE; EXPRESSION; SYNTHASE; DIFFERENTIATION; NEUROGENESIS; NEUROTROPHIN-3; NICHE; BDNF; DEFICITS;
D O I
10.1016/j.neuron.2014.06.015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:572 / 585
页数:14
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