中樞神經(jīng)系統(tǒng)損傷如脊髓損傷的修復是現(xiàn)代臨床醫(yī)學的重要難題。神經(jīng)干細胞移植治療中樞神經(jīng)損傷是一種很有希望的治療手段,。但是無論是內(nèi)源神經(jīng)干細胞還是移植的外源神經(jīng)干細胞在中樞神經(jīng)損傷處神經(jīng)分化都很少,，而絕大部分分化成膠質(zhì)細胞,，甚至形成膠質(zhì)疤痕,。戴建武課題組最近在神經(jīng)再生研究中取得重要進展。發(fā)現(xiàn)了中樞鞘蛋白抑制因子的新功能,。除了具有已知的抑制神經(jīng)元軸突再生的功能,，在調(diào)節(jié)神經(jīng)干細胞分化過程中發(fā)揮重要作用外，還具有很強的膠質(zhì)細胞誘導作用,。其中Nogo-A的再生活性片段Nogo-66具有明顯的誘導神經(jīng)干細胞向膠質(zhì)細胞分化的作用,，同時也抑制向神經(jīng)元的分化。Nogo-66的膠質(zhì)分化誘導作用是通過NgR介導的,。誘導信號傳遞到細胞內(nèi)后,，激活mTOR和STAT3的磷酸化，Nogo-66能促進mTOR和STAT3形成復合物,，然后STAT3轉(zhuǎn)導到細胞核啟動膠質(zhì)細胞的分化,。他們的發(fā)現(xiàn)為研究神經(jīng)干細胞的分化調(diào)控，移植治療和再生修復提供了新的觀點和視野,，結(jié)果發(fā)表在最近的PLoS ONE上。
另外,，嗅鞘細胞是存在于嗅球中的一類特殊的膠質(zhì)細胞,。近年來，嗅鞘細胞移植治療脊髓損傷成為一大熱點,。雖然嗅鞘細胞在治療脊髓損傷過程中,，對于促進受損神經(jīng)元的軸突再生具有一定效果，但結(jié)果并不顯著,。戴建武課題組最近研究發(fā)現(xiàn),，嗅鞘細胞能明顯促進神經(jīng)干細胞的增殖，但抑制神經(jīng)干細胞向神經(jīng)元的分化,。發(fā)現(xiàn)嗅鞘細胞通過調(diào)節(jié)特定信號通路促進神經(jīng)干細胞增殖同時抑制神經(jīng)元分化,。這將為我們?nèi)嬖u價嗅鞘細胞移植對神經(jīng)再生的作用，提高脊髓損傷治療治療效果提供依據(jù),。報道相關(guān)結(jié)果的論文被NEUROSCIENCE 接受,。
生物谷推薦相關(guān)論文：
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.
