Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells
Conditional deletion of Stat3 promotes neurogenesis and inhibits astrogliogenesis in neural stem cells
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DOI：
10.1016/j.bbrc.2010.03.092
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发表时间：
2010-04-09
影响因子：
3.1
通讯作者：
Sakanaka, Masahiro
中科院分区：
文献类型：
--
作者：
Cao, Fang;Hata, Ryuji;Sakanaka, Masahiro
虽然信号换能器和转录激活因子3 （Stat3）在决定神经干细胞（NSC）的命运中起着至关重要的作用，但Stat3在NSC功能中具有多种作用，而且在神经元存活和肿瘤发生中起着重要作用。为了研究Stat3对NSC的整体影响，从Stat3（flox/flox）小鼠胚胎（E14-15d）中分离出NSC，其中Stat3等位基因两侧都有LoxP位点，将分离的NSC接种表达Cre重组酶（Ad nCre）的腺病毒载体或表达β -半乳糖苷酶（Ad. nlz）的对照腺病毒载体。3天后，实时荧光定量PCR （qPCR）分析显示，nCre在NSC启动子中消除了sun 3 mRNA的表达，证实了nCre的过表达抑制了急性反应元件（APRE）的反激活，阻断了NSC中Stat3的功能。Western blot分析和免疫细胞化学分析显示，NSC中Stat3的消除促进了神经发生，抑制了星形胶质细胞的发生。qPCR分析显示，NSC中Stat3的消除通过下调notch来促进神经发生，抑制星形胶质细胞的发生。， notch2和hes5，但不含hes1 mRNA表达(C) 2010 Elsevier Inc版权所有
Although signal transducer and activator of transcription 3 (Stat3) plays crucial roles in the determination of neural stem cell (NSC) fate, Stat3 has multiple roles in NSC function Moreover, Stat3 plays important roles in neuronal survival and tumorigenesis. To investigate the overall effects of Stat3 on NSC fate, NSC were isolated from Stat3(flox/flox) mouse embryos (E14-15d), in which both Stat3 alleles are flanked by LoxP sites Isolated NSC was inoculated with an adenovirus vector expressing Cre recombinase (Ad nCre) or a control adenovirus vector expressing beta-galactosidase (Ad.nLz). Three days later, quantitative real-time PCR (qPCR) analysis revealed that treatment with Ad.nCre eliminated sun 3 mRNA expression in NSC Promoter assay confirmed that overexpression of nCre inhibited transactivation of acute responsive element (APRE) and blocked Stat3 function in NSC Moreover, Western blot analysis and immunocytochemical analysis revealed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis In addition, we investigated the effects of Stat3 elimination in NSC on the mRNA expression of Notch family members and bHLH factors Consequently, qPCR analysis showed that elimination of Stat3 in NSC promoted neurogenesis and inhibited astrogliogenesis through down-regulation of notch!, notch2 and hes5, but not hes1 mRNA expression (C) 2010 Elsevier Inc All rights reserved