State Key Laboratory of Neuroscience, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Elife. 2019 Aug 23;8:e48660. doi: 10.7554/eLife.48660.
Gliosis defined as reactive changes of resident glia is the primary response of the central nervous system (CNS) to trauma. The proliferation and fate controls of injury-reactivated glia are essential but remain largely unexplored. In zebrafish optic tectum, we found that stab injury drove a subset of radial glia (RG) into the cell cycle, and surprisingly, proliferative RG responding to sequential injuries of the same site were distinct but overlapping, which was in agreement with stochastic cell-cycle entry. Single-cell RNA sequencing analysis and functional assays further revealed the involvement of Notch/Delta lateral inhibition in this stochastic cell-cycle entry. Furthermore, the long-term clonal analysis showed that proliferative RG were largely gliogenic. Notch inhibition of reactive RG, not dormant and proliferative RG, resulted in an increased production of neurons, which were short-lived. Our findings gain new insights into the proliferation and fate controls of injury-reactivated CNS glia in zebrafish.
神经胶质细胞增生定义为固有神经胶质的反应性变化，是中枢神经系统（CNS）对创伤的主要反应。损伤激活的神经胶质细胞的增殖和命运控制是必不可少的，但在很大程度上仍未得到探索。在斑马鱼视顶盖中，我们发现刺伤驱动了一小部分放射状胶质细胞（RG）进入细胞周期，令人惊讶的是，对同一部位的连续损伤有反应的增殖 RG 是不同但重叠的，这与随机细胞周期进入一致。单细胞 RNA 测序分析和功能测定进一步表明 Notch/Delta 侧向抑制参与了这种随机的细胞周期进入。此外，长期的克隆分析表明，增殖 RG 主要是神经胶质源性的。Notch 对反应性 RG 的抑制，而不是休眠和增殖 RG 的抑制，导致神经元的产生增加，这些神经元是短暂存在的。我们的发现为斑马鱼中枢神经系统损伤激活的神经胶质细胞的增殖和命运控制提供了新的见解。
