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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4
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Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4

机译:用Klf4的化学互补将鼠成纤维细胞重编程为诱导多能干细胞

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摘要

Ectopic expression of defined transcription factors can reprogram somatic cells to induced pluripotent stem (iPS) cells, but the utility of iPS cells is hampered by the use of viral delivery systems. Small molecules offer an alternative to replace virally transduced transcription factors with chemical signaling cues responsible for re-programming. In this report we describe a small-molecule screening platform applied to identify compounds that functionally replace the reprogramming factor Klf4. A series of small-molecule scaffolds were identified that activate Nanog expression in mouse fibroblasts transduced with a subset of reprogramming factors lacking Klf4. Application of one such molecule, kenpaullone, in lieu of Klf4 gave rise to iPS cells that are indistinguishable from murine embryonic stem cells. This experimental platform can be used to screen large chemical libraries in search of novel compounds to replace the reprogramming factors that induce pluripotency. Ultimately, such compounds may provide mechanistic insight into the reprogramming process.
机译:定义的转录因子的异位表达可以将体细胞重编程为诱导性多能干(iPS)细胞,但是iPS细胞的实用性因使用病毒递送系统而受到阻碍。小分子提供了一种替代方案,可以用负责重新编程的化学信号提示替代病毒转导的转录因子。在本报告中,我们描述了一个小分子筛选平台,该平台用于鉴定功能上替代重编程因子Klf4的化合物。鉴定了一系列小分子支架,这些支架激活小鼠成纤维细胞中用缺乏Klf4的重编程因子子集转导的Nanog表达。代替Klf4,使用一种这样的分子kenpaullone产生了与小鼠胚胎干细胞无法区分的iPS细胞。该实验平台可用于筛选大型化学文库,以寻找新型化合物来替代诱导多能性的重编程因子。最终,此类化合物可为重编程过程提供机械洞察力。

著录项

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  • 作者单位

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037;

    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

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

    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121;

    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

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

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

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037;

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037;

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037;

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037;

    lnstitut fur Pharmazeutische Chemie, Technische Universitat Braunschweig, 38106 Braunschweig, Germany;

    Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121;

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121;

    The Skaggs Institute of Chemical Biology and Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037 Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121;

    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;

  • 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

    chemical biology; high-throughput screening; nanog;

    机译:化学生物学;高通量筛选纳克;

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