• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Direct cell reprogramming is a stochastic process amenable to acceleration
【24h】

Direct cell reprogramming is a stochastic process amenable to acceleration

机译：直接细胞重编程是适合加速的随机过程

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

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency.
机译：通过过表达Oct4，Sox2，Klf4和c-Myc转录因子可以将体细胞直接重编程为诱导多能干（iPS）细胞，但是只有少数供体体细胞可以重编程为多能性。在这里，我们证明了通过这些转录因子进行的重编程是一个连续的随机过程，其中几乎所有的小鼠供体细胞在持续生长和转录因子表达时最终都产生了iPS细胞。 p53 / p21途径的额外抑制或Lin28的过度表达增加了细胞分裂速率，并导致iPS细胞形成的动力学加速，与细胞增殖的增加成正比。相反，Nanog过表达主要以细胞分裂速率无关的方式加速重编程。定量分析定义了不同的细胞分裂速率依赖性和非依赖性模式，以加速随机重编程过程，并建议细胞分裂的数目是驱动表观遗传重编程为多能性的关键参数。

著录项

  • 来源
    《Nature》 |2009年第7273期|595-601|共7页
  • 作者

    Jacob Hanna; Krishanu Saha; Bernardo Pando; Jeroen van Zon; Christopher J. Lengner; Menno P. Creyghton; Alexander van Oudenaarden; Rudolf Jaenisch;

  • 作者单位

    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

    The Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);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