Analysis of the molecular mechanisms regulating the maintenance of multipotency and the dedifferentiation of neural stem cells

神经干细胞多能性维持和去分化的分子机制分析

• 批准号: 20610001
• 负责人: OHTSUKA Toshiyuki
• 金额: $ 2.91万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20610001/
• 关键词: 発生・分化; 脳・神経; 神経科学; 再生医学; 幹細胞

To shed light on the temporal and regional differences of embryonic neural stem cells, we sorted the green fluorescent protein (GFP)-positive neural stem cells from the telencephalon of pHes1-d2EGFP transgenic mouse embryos at different developmental stages, and from different regions of the telencephalon of the transgenic mice at embryonic day 11.5, and performed gene expression profiling. Among dozens of transcription factors differentially expressed by cells in the ventricular zone during the course of development, several of them exhibited the activity to inhibit neuronal differentiation when overexpressed. Furthermore, knock-down of Tcf3 or Klf15 led to accelerated neuronal differentiation, suggesting that these transcription factors play critical roles in the maintenance of neural stem cells at early and late embryonic stages, respectively.

为了揭示胚胎神经干细胞的时间和区域差异，我们从不同发育阶段的pHes1-d2EGFP转基因小鼠胚胎的端脑以及胚胎11.5天的转基因小鼠端脑的不同区域中分选了绿色荧光蛋白（GFP）阳性的神经干细胞，并进行了基因表达谱分析。在心室区细胞在发育过程中差异表达的数十种转录因子中，其中一些转录因子在过度表达时表现出抑制神经元分化的活性。此外，Tcf3或Klf15的敲除导致神经元分化加速，表明这些转录因子分别在早期和晚期胚胎阶段的神经干细胞的维持中发挥着关键作用。

项目成果

大脳新皮質発生における神経幹細胞の遺伝子発現プロファイリング

新皮质发育过程中神经干细胞的基因表达谱

• 发表时间: 2010
• 作者: 水澤直樹;酒田慎也;桜井勇;久保田寿子;佐藤直樹;和田元;成川礼;佐々木徹;大塚俊之
• 通讯作者: 大塚俊之

Gene expression profiling of neural stem cells during cortical development

皮质发育过程中神经干细胞的基因表达谱

• 发表时间: 2010
• 作者: 水澤直樹;酒田慎也;桜井勇;佐藤直樹;和田元;Toshiyuki Ohtsuka
• 通讯作者: Toshiyuki Ohtsuka

Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain

• DOI: 10.1038/nn.2185
• 发表时间: 2008-10-01
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Imayoshi, Itaru;Sakamoto, Masayuki;Kageyama, Ryoichiro
• 通讯作者: Kageyama, Ryoichiro

Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline

• DOI: 10.1242/dev.021535
• 发表时间: 2008-08-01
• 期刊: DEVELOPMENT
• 影响因子: 4.6
• 作者: Imayoshi, Itaru;Shimogori, Tomomi;Kageyama, Ryoichiro
• 通讯作者: Kageyama, Ryoichiro

The first Hesl dimer inhibitors from natural products.

第一个来自天然产物的 Hesl 二聚体抑制剂。

• 发表时间: 2009
• 期刊: Chemistry Letters
• 影响因子: 1.6
• 作者: Arai;M.;Masada;A.;Ohtsuka;T.;Kageyama;R.;and Ishibashi;M.
• 通讯作者: M.