Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction
Endothelial NT-3 Delivered by Vasculature and CSF Promotes Quiescence of Subependymal Neural Stem Cells through Nitric Oxide Induction
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DOI：
10.1016/j.neuron.2014.06.015
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发表时间：
2014-08-06
期刊：
影响因子：
16.2
通讯作者：
Farinas, Isabel
中科院分区：
文献类型：
--
作者：
Delgado, Ana C.;Ferron, Sacri R.;Farinas, Isabel
成体神经干细胞（NSCs）与支持性血管系统的相互作用对它们的维持和功能至关重要，尽管分子细节仍在研究中。神经营养因子（NT）-3属于NT家族的营养因子，以其促进神经元存活的作用而闻名。在这里，我们表明，NT-3的脑和脉络丛毛细血管的内皮细胞产生和分泌的神经干细胞在小鼠室管膜下龛的静止和长期维持所需的。从灌洗脉管系统和脑脊液（CSF）摄取NT-3诱导存在于NSC中的内皮一氧化氮（NO）合酶的快速磷酸化，导致NO的产生，其随后充当细胞生长抑制因子。我们的研究结果确定了干细胞和血管系统/CSF隔室之间的一种新的相互作用，这种相互作用是由神经营养因子的前所未有的作用介导的，并表明干细胞可以调节其自身的静止，以响应内皮分泌的分子。
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.