【摘 要】
：
Notch信号通路作为重要的信号转导系统在细胞增殖、分化中发挥重要的调控作用.在神经系统的发育中,经典Notch信号通路通过其下游关键转录因子RBP-J及效应分子维持着神经干细胞自我更新、增殖与分化之间的平衡,对细胞分化命运起决定性作用.在我们的工作中,首先构建了神经干细胞特异性RBP-J基因敲除小鼠,并通过microRNA基因芯片对比敲除小鼠与对照小鼠神经干细胞中microRNA的表达差异,筛选
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Notch信号通路作为重要的信号转导系统在细胞增殖、分化中发挥重要的调控作用.在神经系统的发育中,经典Notch信号通路通过其下游关键转录因子RBP-J及效应分子维持着神经干细胞自我更新、增殖与分化之间的平衡,对细胞分化命运起决定性作用.在我们的工作中,首先构建了神经干细胞特异性RBP-J基因敲除小鼠,并通过microRNA基因芯片对比敲除小鼠与对照小鼠神经干细胞中microRNA的表达差异,筛选出了一组与神经干细胞特性相关的microRNA分子.在体外实验中,我们从E14.5天的胎鼠端脑获得神经干细胞,在转染了miR-A的mimie/inhibitor之后,通过做神经球克隆形成等实验,发现miR-A mimic组神经干细胞形成的神经球数目增多,inhibitor组形成的神经球数目减少,而增殖与分化指标未见显著差异.在体内实验中,我们通过胚胎侧脑室电穿孔转染在神经干细胞中过表达miR-A,观察到神经干细胞标志物有表达上调的趋势.体内体外实验共同提示Notch信号通路可能通过调控miR-A维持神经干细胞的干性并进一步调控神经系统的发育.
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