长链非编码RNA Vof-16调控脊髓内源性神经干细胞参与脊髓损伤修复的机制研究

内源性脊髓神经干细胞（SC-NSCs）是参与脊髓损伤（SCI）后神经发生的关键，但其调控机制未明。本项目前期发现，长链非编码RNA缺血相关因子Vof-16（Vof-16）在SCI后表达上调，抑制其表达能促进SCI后神经修复和功能改善，并增加体外低氧培养的SC-NSCs存活、增殖及向少突胶质细胞和神经元分化。故推测Vof-16可调控SC-NSCs生物学行为并影响其参与SCI修复。本项目拟建立氧糖剥夺细胞模型，明确Vof-16表达变化对体外培养SC-NSCs的影响；鉴定Vof-16的结合蛋白，探讨其通过结合蛋白影响SC-NSCs表型变化的潜在机制；采用CRISPR/Cas9等构建的Vof-16条件性敲除的转基因大鼠造模，分析Vof-16调控SC-NSCs生物学行为变化的作用机制及其对SCI修复的影响。本研究有助于揭示SC-NSCs修复SCI的内在调控机制，并为治疗SCI提供新的靶点和策略。

Endogenous spinal cord neural stem cells(SC-NSCs) are the key to neurogenesis after spinal cord injury（SCI）. However, the regulatory mechanisms of them are unknown. In previous research, we have found that long non-coding RNA ischemia-related factor Vof-16（Vof-16） was up-regulated after SCI. Inhibition of its expression could promote nerve repair and function improvement after SCI, increase the survival and proliferation of SC-NSCs under hypoxia culture and induce differentiation of SC-NSCs into oligodendrocytes and neurons in vitro. Therefore, it can speculate that Vof-16 may regulate the biological behavior changes of SC-NSCs and influence the participation of SC-NSCs in the repair of injured spinal cord. Hence, this project aims to establish oxygen-glucose deprivation cell models to definite the effects of the expression changes of Vof-16 on SC-NSCs cultured in vitro; to identify Vof-16 binding proteins and investigate their potential mechanisms of affecting the phenotype changes of SC-NSCs by binding proteins; to analyze the molecular mechanisms of the biological behavior changes of SC-NSCs regulated by Vof-16 and the effects of them on SCI repair through using transgenic rat models with conditional knockout of Vof-16 constructed by CRISPR/Cas9. This study is helpful to reveal the intrinsic regulatory mechanism of SC NSCs in repairing SCI, and provides new targets and strategies for the treatment of SCI.