Suppression of Stat3 promotes neurogenesis in cultured neural stem cells
Suppression of Stat3 promotes neurogenesis in cultured neural stem cells
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DOI：
10.1002/jnr.20561
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发表时间：
2005-07-15
影响因子：
4.2
通讯作者：
Sakanaka, M
中科院分区：
文献类型：
--
作者：
Gu, F;Hata, R;Sakanaka, M
为了研究信号换能器和转录激活因子3 （Stat3）对神经干细胞命运的影响，我们用表达Stat3显性阴性形式（Stat3F）的腺病毒载体接种干细胞。一天后，启动子实验显示转染细胞的转录水平显著降低。3 d后，Western blot和免疫细胞化学分析显示，转染细胞中微管相关蛋白（MAP）2蛋白水平和map2阳性细胞数量显著升高，胶质原纤维酸性蛋白（GFAP）蛋白水平和GFAP阳性细胞数量显著降低。此外，在接种Stat3F 3天后，Notch家族成员Notch1、2和3以及抑制性碱性螺旋-环-螺旋（bHLH）因子Hes5、Id2和Id3的mRNA水平均显著下调；然而，bHLH决定因子（Math1和Neurogenin3）和bHLH分化因子（NeuroD1和NeuroD2）的mRNA水平显著上调。这些数据表明，抑制Stat3直接诱导神经干细胞的神经发生，并抑制星形胶质细胞的发生。(c) 2005 Wiley-Liss, Inc。
To investigate the effects of signal transducer and activator of transcription 3 (Stat3) on neural stem cell fate, stem cells were inoculated with an adenovirus vector expressing dominant negative form of Stat3 (Stat3F). One day later, a promoter assay revealed significant reduction of the transcriptional level in the transfected cells. Three days later, Western blot analysis and immunocytochemical analysis revealed that the protein level of microtubule-associated protein (MAP)2 and the number of MAP2-positive cells were increased significantly in the transfected cells whereas the protein level of glial fibrillary acidic protein (GFAP) and the number of GFAP-positive cells were decreased significantly. In addition, mRNA levels of Notch family members (Notch1, 2, and 3) and of inhibitory basic helix-loop-helix (bHLH) factors (Hes5, Id2, and Id3) were significantly downregulated at 3 days after viral inoculation with Stat3F; however, mRNA levels of bHLH determination factors (Math1 and Neurogenin3) and bHLH differentiation factors (NeuroD1 and NeuroD2) were significantly upregulated. These data indicated that suppression of Stat3 directly induced neurogenesis and inhibited astrogliogenesis in neural stem cells. (c) 2005 Wiley-Liss, Inc.