Interferon-gamma inhibits the neuronal differentiation of neural progenitor cells by inhibiting the expression of Neurogenin2 via the JAK/STAT1 pathway
Interferon-gamma inhibits the neuronal differentiation of neural progenitor cells by inhibiting the expression of Neurogenin2 via the JAK/STAT1 pathway
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DOI：
10.1016/j.bbrc.2015.08.104
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发表时间：
2015-10-09
影响因子：
3.1
通讯作者：
Kim, Sunyoung
中科院分区：
文献类型：
--
作者：
Ahn, Jyhyun;Lee, Junsub;Kim, Sunyoung
干扰素-γ是宿主免疫细胞感染后释放的重要细胞因子之一。尽管干扰素-γ在宿主免疫反应中具有重要作用(S)，但目前还没有关于干扰素-γ对脑发育影响的体内研究，许多体外研究的结果也是有争议的。本研究旨在探讨干扰素-γ对胚胎神经发生的影响。用干扰素-γ处理E14.5小鼠神经前体细胞后，TuJ1阳性未成熟神经元的百分率降低，而巢蛋白阳性的神经前体细胞百分率增加。在体内也得到了类似的结果。用JAK抑制剂处理NC或下调STAT1的表达可消除干扰素-γ介导的神经发生抑制。有趣的是，前神经基因之一Neurogenin2(Neurog2)的表达在干扰素-伽马处理后被显著抑制，而过度表达Neurog2的细胞对干扰素-伽马没有反应。综上所述，我们的结果表明，干扰素-γ通过JAK/STAT1途径负向调节Neurog2的表达，从而抑制神经干细胞的神经元分化。我们的发现可能为深入了解干扰素-γ在胚胎脑发育中的作用提供依据。(C)2015 Elsevier Inc.保留所有权利。
Interferon-gamma (IFN-gamma) is one of the critical cytokines released by host immune cells upon infection. Despite the important role(s) of IFN-gamma in host immune responses, there has been no in vivo study regarding the effects of IFN-gamma on brain development, and the results from many in vitro studies are controversial. In this study, the effects of IFN-gamma on embryonic neurogenesis were investigated. Treatment of E14.5 mouse neural progenitor cells (NPCs) with IFN-gamma resulted in a decrease in the percentage of TuJ1-positive immature neurons but an increase in the percentage of Nestin-positive NPCs. Similar results were obtained in vivo. Treatment of NPCs with a JAK inhibitor or the knockdown of STAT1 expression abrogated the IFN-gamma-mediated inhibition of neurogenesis. Interestingly, the expression of one of proneural genes, Neurogenin2 (Neurog2) was dramatically inhibited upon IFN-gamma treatment, and cells overexpressing Neurog2 did not respond to IFN-gamma. Taken together, our results demonstrate that IFN-gamma inhibits neuronal differentiation of NPCs by negatively regulating the expression of Neurog2 via the JAK/STAT1 pathway. Our findings may provide an insight into the role of IFN-gamma in the development of embryonic brain. (C) 2015 Elsevier Inc. All rights reserved.