Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function
Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function
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DOI：
10.1096/fj.08-105908
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发表时间：
2008-11
期刊：
影响因子：
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通讯作者：
Pengxiang Zhu;R. Hata;Fang Cao;Feng Gu;Y. Hanakawa;K. Hashimoto;M. Sakanaka
中科院分区：
文献类型：
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作者：
Pengxiang Zhu;R. Hata;Fang Cao;Feng Gu;Y. Hanakawa;K. Hashimoto;M. Sakanaka
神经干细胞（NSC）的分化和增殖受其内在特性（例如，转录因子、表观遗传因子和microRNA调节）和来自NSC周围微环境的细胞外在特性（例如，细胞因子、生长因子和细胞-细胞接触）。最近，人们对阐明微环境对NSC的影响机制产生了极大的兴趣，特别是NSC与附近其他类型细胞之间的细胞-细胞接触。在这项研究中，我们研究了小胶质细胞（Mi）细胞是否影响神经干细胞的命运。共培养研究表明，分化的Mi细胞通过旁分泌作用促进星形胶质细胞的形成和神经干细胞的维持。这种小胶质细胞诱导的星形胶质细胞生成被AG 490和Stat 3和SOCS 3的显性阴性形式的过表达抑制。启动子分析显示Mi细胞反式激活NSC中的Stat 3功能。基因表达研究显示，NSC中Notch家族成员（notchl-3）和sox 9的mRNA被Mi细胞显著上调，并且这种上调被AG 490抑制。这些结果表明，分枝Mi细胞通过激活Stat 3功能并经由notch和sox 9信号通路促进星形胶质细胞生成和NSC的维持。Zhu，P.，中国科学院院士，Hata河，Cao，F.，顾，F.，Hanakawa，Y.，Hashimoto，K.，Sakanaka，M.分支小胶质细胞通过激活Stat 3功能促进星形胶质细胞生成和维持神经干细胞。FASEB J. 22，3866-3877（2008）
The differentiation and proliferation of neural stem cells (NSCs) are regulated by a combination of their intrinsic properties (e.g., transcription factors, epigenetic factors, and microRNA regulation) and cell‐extrinsic properties from the microenvironment around NSC (e.g., cytokines, growth factors, and cell‐cell contact). Recently, there has been a great interest in clarifying the mechanism of the influence of the microenvironment on NSCs, especially cell‐cell contact between NSCs and other types of cells nearby. In this study, we investigated whether microglial (Mi) cells influence the fate of NSCs. Coculture study showed that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs through their paracrine effects. This microglia‐induced astrogliogenesis was inhibited by AG490 and by overexpression of the dominant‐negative form of Stat3 and SOCS3. Promoter assay revealed transactivation of Stat3 function in NSCs by Mi cells. Gene expression study revealed that mRNA of Notch family members (notchl‐3) and sox9 in NSCs was significantly upregulated by Mi cells, and this up‐regulation was inhibited by AG490. These results demonstrated that ramified Mi cells promoted astrogliogenesis and maintenance of NSCs by activating Stat3 function and via notch and sox9 signaling pathways.— Zhu, P., Hata, R., Cao, F., Gu, F., Hanakawa, Y., Hashimoto, K., Sakanaka, M. Ramified microglial cells promote astrogliogenesis and maintenance of neural stem cells through activation of Stat3 function. FASEB J. 22, 3866–3877 (2008)