控制成年静息态神经干细胞激活的分子开关

A molecular switch that controls activation of adult quiescent neural stem cells

上海交通大学基础医学院解剖学与生理学系徐楠杰研究组发现了能够控制成年静息态神经干细胞激活的分子开关。该研究成果以“A neuronal molecular switch through cell-cell contact that regulates quiescent neural stem cells”为题于2019 年2 月在线发表于Science 子刊Sci Adv。博士研究生董健是论文的第一作者,徐楠杰研究员和上海交通大学医学院附属瑞金医院孙苏亚研究员是论文的共同通信作者。上海交通大学医学院是论文的通信单位。

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.