Nongenetic optical modulation of neural stem cell proliferation and neuronal/glial differentiation
Nongenetic optical modulation of neural stem cell proliferation and neuronal/glial differentiation
复制标题
神经干细胞增殖和神经元/神经胶质分化的非遗传光调节
DOI：
10.1016/j.biomaterials.2019.119539
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发表时间：
2019
期刊：
影响因子：
14
通讯作者：
Li Xi
中科院分区：
文献类型：
--
作者：
Wang Meitian;Xu Zhiliang;Liu Qiao;Sun Wenjie;Jiang Baichun;Yang Kun;Li Jiangxia;Gong Yaoqin;Liu Qiji;Liu Duo;Li Xi
光刺激已广泛用于神经调节。然而，现有的光遗传学技术需要靶细胞或组织的遗传改变。在这里，我们报告说，神经干细胞（NSC）的组成表达蓝/红光敏感的光感受器。神经干细胞向神经元或神经胶质细胞的增殖和调节具有波长特异性。我们的研究结果显示，在低功率蓝色单色光照射（455 nm，300 μW/cm 2）下，细胞增殖增加4.3倍，星形胶质细胞分化增加2.7倍。黑视蛋白（Opn 4）/瞬时受体电位通道6（TRPC 6）非视觉视蛋白充当对蓝光照射的关键光感受器响应。二维凝胶电泳结合质谱进一步强调了Jun激活结构域结合蛋白1（Jab 1）作为一种新的和特定的调制器在蓝光照射诱导的光转导途径。静止的成体神经干细胞存在于哺乳动物大脑的特定区域。因此，我们发现在这些区域表达的黑视素/TRPC 6和通过光纤的蓝光刺激可以直接刺激NSCsin体内。上转换纳米粒子（UCNPs）将深穿透近红外（NIR）光转换为特定波长的可见光。因此，我们证明了UCNP介导的近红外光可以用于以侵入性较小的方式调节体内NSC分化。在未来，这种光触发的神经干细胞系统将使非遗传性和非侵入性神经调节具有治疗中枢神经系统疾病的潜力。
Photostimulation has been widely used in neuromodulation. However, existing optogenetics techniques require genetic alternation of the targeted cell or tissue. Here, we report that neural stem cells (NSCs) constitutionally express blue/red light-sensitive photoreceptors. The proliferation and regulation of NSCs to neuronal or glial cells are wavelength-specific. Our results showed a 4.3-fold increase in proliferation and 2.7-fold increase in astrocyte differentiation for cells under low-power blue monochromatic light exposure (455 nm, 300 μW/cm2). The melanopsin (Opn4)/transient receptor potential channel 6 (TRPC6) non-visual opsin serves as a key photoreceptor response to blue light irradiation. Two-dimensional gel electrophoresis coupled with mass spectrometry further highlighted the Jun activation domain-binding protein 1 (Jab1) as a novel and specific modulator in phototransduction pathways induced by blue light exposure. Quiescent adult NSCs reside in specific regions of the mammalian brain. Therefore, we showed that melanopsin/TRPC6 expressed in these regions and blue light stimulation through optical fibers could directly stimulate the NSCsin vivo. Upconversion nanoparticles (UCNPs) converted deep-penetrating near-infrared (NIR) light into specific wavelengths of visible light. Accordingly, we demonstrated that UCNP-mediated NIR light could be used to modulatein vivoNSC differentiation in a less invasive manner. In the future, this light-triggered system of NSCs will enable nongenetic and noninvasive neuromodulation with therapeutic potential for central nervous system diseases.