A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells
A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells
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通过细胞与细胞接触调节静止神经干细胞的神经元分子开关
DOI：
10.1126/sciadv.aav4416
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发表时间：
2019-02-01
期刊：
影响因子：
13.6
通讯作者：
Xu, Tian-Le
中科院分区：
文献类型：
--
作者：
Dong, Jian;Pan, Yuan-Bo;Xu, Tian-Le
兴奋性海马颗粒细胞调节自发运动中静止神经干细胞的激活和转换。放射状神经干细胞（radial neural stem cells，rNSCs）的静止受环境刺激的调节。然而，很少有人知道神经原性龛如何耦合外部信号来调节静止的rNSCs的激活和转换。在这里，我们揭示了自愿运行后，海马齿状颗粒细胞（GC）的长期兴奋导致激活的成年rNSCs在颗粒下区，从而产生新生神经元。出乎意料的是，这些兴奋的GC神经元在NSC中的作用取决于局部小生境中的直接GC-rNSC相互作用，这是通过下调肝配蛋白-B3（GC膜结合配体）和减弱相邻rNSC中的跨细胞EphB 2激酶依赖性信号传导。此外，组成型活性EphB 2激酶在运行期间维持rNSC的静止。因此，这些研究结果阐明了GC兴奋性在外部环境下的成年rNSCs的生理意义，并表明通过细胞-细胞接触的rNSCs的功能转变的钥匙锁开关调节。
Excitatory hippocampal granule cells regulate activation and transition of quiescent neural stem cells during voluntary exercise. The quiescence of radial neural stem cells (rNSCs) in adult brain is regulated by environmental stimuli. However, little is known about how the neurogenic niche couples the external signal to regulate activation and transition of quiescent rNSCs. Here, we reveal that long-term excitation of hippocampal dentate granule cells (GCs) upon voluntary running leads to activation of adult rNSCs in the subgranular zone and thereby generation of newborn neurons. Unexpectedly, the role of these excited GC neurons in NSCs depends on direct GC-rNSC interaction in the local niche, which is through down-regulated ephrin-B3, a GC membrane–bound ligand, and attenuated transcellular EphB2 kinase–dependent signaling in the adjacent rNSCs. Furthermore, constitutively active EphB2 kinase sustains the quiescence of rNSCs during running. These findings thus elucidate the physiological significance of GC excitability on adult rNSCs under external environments and indicate a key-lock switch regulation via cell-cell contact for functional transition of rNSCs.