...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a
【24h】

Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a

机译：Neurogenin3通过诱导Cdkn1a抑制内分泌祖细胞的增殖

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

During organogenesis, the final size of mature cell populations depends on their rates of differentiation and expansion. Because transient expression of Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates their differentiation to mature islet cells, we examined the role of Neurog3 in cell cycle control during this process. We found that mitotically active pancreatic progenitor cells in mouse embryos exited the cell cycle after the initiation of Neurog3 expression. Transcriptome analysis demonstrated that the Neurog3-expressing cells dramatically up-regulated the mRNA encoding cyclin-dependent kinase inhibitor 1a (Cdkn1a). In Neurog3 null mice, the islet progenitor cells failed to activate Cdkn1a expression and continued to proliferate, showing that their exit from the cell cycle requires Neurog3. Furthermore, induced transgenic expression of Neurog3 in mouse β-cells in vivo markedly decreased their proliferation, increased Cdkn1a levels, and eventually caused profound hyperglycemia. In contrast, in Cdkn1a null mice, proliferation was incompletely suppressed in the Neurog3-expressing cells. These studies reveal a crucial role for Neurog3 in regulating the cell cycle during the differentiation of islet cells and demonstrate that the subsequent down-regulation of Neurog3 allows the mature islet cell population to expand.
机译：在器官发生过程中，成熟细胞群的最终大小取决于它们的分化和扩增速率。由于Neurogenin3（Neurog3）在发育中的胰腺祖细胞中的瞬时表达启动了它们向成熟胰岛细胞的分化，因此我们在此过程中检查了Neurog3在细胞周期控制中的作用。我们发现，在启动Neurog3表达后，小鼠胚胎中的有丝分裂活跃的胰腺祖细胞退出了细胞周期。转录组分析表明，表达Neurog3的细胞显着上调了编码细胞周期蛋白依赖性激酶抑制剂1a（Cdkn1a）的mRNA的表达。在Neurog3空小鼠中，胰岛祖细胞未能激活Cdkn1a表达并继续增殖，表明它们退出细胞周期需要Neurog3。此外，在小鼠β细胞体内诱导的Neurog3转基因表达显着降低了它们的增殖，增加了Cdkn1a水平，并最终引起了严重的高血糖症。相反，在Cdkn1a无效小鼠中，在Neurog3表达细胞中增殖不完全被抑制。这些研究揭示了Neurog3在胰岛细胞分化过程中调控细胞周期中的关键作用，并证明了随后Neurog3的下调使成熟的胰岛细胞群得以扩展。

著录项

  • 来源
  • 作者

    Takeshi Miyatsuka; Yasuhiro Kosaka; Hail Kim; Michael S. German;

  • 作者单位

    Diabetes Center, Hormone Research Institute and Department of Medicine, University of California, San Francisco, CA 94143;

    Diabetes Center, Hormone Research Institute and Department of Medicine, University of California, San Francisco, CA 94143;

    Diabetes Center, Hormone Research Institute and Department of Medicine, University of California, San Francisco, CA 94143;

    Diabetes Center, Hormone Research Institute and Department of Medicine, University of California, San Francisco, CA 94143;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号