Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
J Neurosci. 2012 Mar 7;32(10):3376-87. doi: 10.1523/JNEUROSCI.4248-11.2012.
Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons remains largely unknown. We isolated NSCs and their progeny in the adult DG using transgenic mice expressing a GFP reporter under the control of the Sox2 promoter (labeling NSCs) and transgenic mice expressing a DsRed reporter under the control of the doublecortin (DCX) promoter (labeling immature neurons). Transcriptome analyses revealed distinct gene expression profiles between NSCs and immature neurons. Among the genes that were expressed at significantly higher levels in DG NSCs than in immature neurons was the growth factor insulin-like growth factor 2 (IGF2). We show that IGF2 selectively controls proliferation of DG NSCs in vitro and in vivo through AKT-dependent signaling. Thus, by gene expression profiling of NSCs and their progeny, we have identified IGF2 as a novel regulator of adult neurogenesis.
神经干细胞 (NSCs) 在海马齿状回 (DG) 中终生产生神经元。NSCs 和未成熟神经元之间的基因表达特征有何不同，在很大程度上仍不清楚。我们使用表达 GFP 报告基因的转基因小鼠（受 Sox2 启动子控制）和表达 DsRed 报告基因的转基因小鼠（受双皮质素 (DCX) 启动子控制），在成年 DG 中分离 NSCs 及其祖细胞（标记 NSCs）和未成熟神经元）。转录组分析显示 NSCs 和未成熟神经元之间存在明显不同的基因表达谱。在 DG NSCs 中表达水平明显高于未成熟神经元的基因中，有一种是生长因子胰岛素样生长因子 2 (IGF2)。我们表明，IGF2 通过 AKT 依赖性信号通路选择性控制 DG NSCs 的体外和体内增殖。因此，通过 NSCs 及其祖细胞的基因表达谱分析，我们将 IGF2 鉴定为成体神经发生的一种新的调节因子。
