中科院遺傳所戴建武課題組最近在神經(jīng)再生研究中取得重要進(jìn)展,。他們發(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(xì)胞分化過程中發(fā)揮重要作用外,還具有很強的膠質(zhì)細(xì)胞誘導(dǎo)作用,。其中Nogo-A的再生活性片段Nogo-66具有明顯的誘導(dǎo)神經(jīng)干細(xì)胞向膠質(zhì)細(xì)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(dǎo)作用是通過NgR介導(dǎo)的,。誘導(dǎo)信號傳遞到細(xì)胞內(nèi)后,,激活mTOR和STAT3的磷酸化,Nogo-66能促進(jìn)mTOR和STAT3形成復(fù)合物,,然后STAT3轉(zhuǎn)導(dǎo)到細(xì)胞核啟動膠質(zhì)細(xì)胞的分化,。他們的發(fā)現(xiàn)為研究神經(jīng)干細(xì)胞的分化調(diào)控、移植治療和再生修復(fù)提供了新的觀點和視野,,結(jié)果發(fā)表在最近的《公共科學(xué)圖書館·綜合》(PLoS ONE)上,。
生物谷推薦原始出處:
(PLoS ONE),doi:10.1371/journal.pone.0001856,,Bin Wang, Jianwu Dai
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.