Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR-STAT3 pathway.
Nogo-66 promotes the differentiation of neural progenitors into astroglial lineage cells through mTOR-STAT3 pathway.
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DOI：
10.1371/journal.pone.0001856
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发表时间：
2008-03-26
期刊：
影响因子：
3.7
通讯作者：
Dai J
中科院分区：
文献类型：
--
作者：
Wang B;Xiao Z;Chen B;Han J;Gao Y;Zhang J;Zhao W;Wang X;Dai J
神经干/祖细胞（neural stem/progenitor cells，NPC）可分化为神经元、星形胶质细胞和少突胶质细胞。NPC被认为是有价值的细胞治疗损伤的中枢神经系统（CNS）。然而，当NPC移植到成年哺乳动物脊髓中时，它们大多分化为胶质细胞谱系。在脊髓损伤期间，内源性NPC也观察到了相同的结果。然而，很少有人知道这种命运决定的NPC的机制。在本研究中，我们发现髓鞘蛋白和Nogo-66促进NPC向胶质细胞系分化。NgR和mTOR-Stat 3通路参与了这一过程。从细胞膜释放NgR或阻断mTOR-STAT 3可以挽救Nogo-66增强的胶质细胞分化。这些结果揭示了Nogo-66在NPC命运决定中的新功能。这一发现可能对CNS发育的理解产生深远的影响，并可能改善CNS损伤的治疗。
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. 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. 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.
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