中枢神经系统损伤如脊髓损伤的修复是现代临床医学的重要难题。神经干细胞移植治疗中枢神经损伤是一种很有希望的治疗手段。但是无论是内源神经干细胞还是移植的外源神经干细胞在中枢神经损伤处神经分化都很少，而绝大部分分化成胶质细胞，甚至形成胶质疤痕。戴建武课题组最近在神经再生研究中取得重要进展。发现了中枢鞘蛋白抑制因子的新功能。除了具有已知的抑制神经元轴突再生的功能，在调节神经干细胞分化过程中发挥重要作用外，还具有很强的胶质细胞诱导作用。其中Nogo-A的再生活性片段Nogo-66具有明显的诱导神经干细胞向胶质细胞分化的作用，同时也抑制向神经元的分化。Nogo-66的胶质分化诱导作用是通过NgR介导的。诱导信号传递到细胞内后，激活mTOR和STAT3的磷酸化，Nogo-66能促进mTOR和STAT3形成复合物，然后STAT3转导到细胞核启动胶质细胞的分化。他们的发现为研究神经干细胞的分化调控，移植治疗和再生修复提供了新的观点和视野，结果发表在最近的PLoS ONE上。
另外，嗅鞘细胞是存在于嗅球中的一类特殊的胶质细胞。近年来，嗅鞘细胞移植治疗脊髓损伤成为一大热点。虽然嗅鞘细胞在治疗脊髓损伤过程中，对于促进受损神经元的轴突再生具有一定效果，但结果并不显著。戴建武课题组最近研究发现，嗅鞘细胞能明显促进神经干细胞的增殖，但抑制神经干细胞向神经元的分化。发现嗅鞘细胞通过调节特定信号通路促进神经干细胞增殖同时抑制神经元分化。这将为我们全面评价嗅鞘细胞移植对神经再生的作用，提高脊髓损伤治疗治疗效果提供依据。报道相关结果的论文被NEUROSCIENCE 接受。
生物谷推荐相关论文：
PLoS ONE 3(3): e1856. doi:10.1371/journal.pone.0001856
Nogo-66 Promotes the Differentiation of Neural Progenitors into Astroglial Lineage Cells through mTOR-STAT3 Pathway
Bin Wang#, Zhifeng Xiao#, Bing Chen, Jin Han, Yuan Gao, Jing Zhang, Wenxue Zhao, Xia Wang, Jianwu Dai*
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
Abstract
Background
Neural stem/progenitor cells (NPCs) can differentiate into neurons, astrocytes and oligodendrocytes. NPCs are considered valuable for the cell therapy of injuries in the central nervous system (CNS). However, when NPCs are transplanted into the adult mammalian spinal cord, they mostly differentiate into glial lineage. The same results have been observed for endogenous NPCs during spinal cord injury. However, little is known about the mechanism of such fate decision of NPCs.
Methodology/Principal Findings
In the present study, we have found that myelin protein and Nogo-66 promoted the differentiation of NPCs into glial lineage. NgR and mTOR-Stat3 pathway were involved in this process. Releasing NgR from cell membranes or blocking mTOR-STAT3 could rescue the enhanced glial differentiation by Nogo-66.
Conclusions/Significance
These results revealed a novel function of Nogo-66 in the fate decision of NPCs. This discovery could have profound impact on the understanding of CNS development and could improve the therapy of CNS injuries.
