...
  • 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 >Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation
【24h】

Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation

机译：Oct4，Sox2，Klf4和c-Myc表达对人类有效iPSC诱导和分化的化学计量和时间要求

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

Human-induced pluripotent stem cells (hiPSCs) are generated from somatic cells by ectopic expression of the 4 reprogramming factors (RFs) Oct-4, Sox2, Klf4, and c-Myc. To better define the stoichiometric requirements and dynamic expression patterns required for successful hiPSC induction, we generated 4 bicistronic lentiviral vectors encoding the 4 RFs co-expressed with discernable fluorescent proteins. Using this system, we define the optimal stoichiometry of RF expression to be highly sensitive to Oct4 dosage, and we demonstrate the impact that variations in the relative ratios of RF expression exert on the efficiency of hiPSC induction. Monitoring of expression of each individual RF in single cells during the course of reprogramming revealed that vector silencing follows acquisition of pluripotent cell markers. Pronounced lentiviral vector silencing was a characteristic of successfully reprogrammed hiPSC clones, but lack of complete silencing did not hinder hiPSC induction, maintenance, or directed differentiation. The vector system described here presents a powerful tool for mechanistic studies of reprogramming and the optimization of hiPSC generation.
机译：人诱导的多能干细胞（hiPSC）是通过异位表达Oct-4，Sox2，Klf4和c-Myc的4种重编程因子（RF）从体细胞中产生的。为了更好地定义成功hiPSC诱导所需的化学计量要求和动态表达模式，我们生成了4个双顺反子慢病毒载体，它们编码与可辨别的荧光蛋白共表达的4个RF。使用此系统，我们将RF表达的最佳化学计量定义为对Oct4剂量高度敏感，并证明RF表达相对比率的变化对hiPSC诱导效率的影响。在重编程过程中对单个RF在单个细胞中的表达的监测表明，载体沉默跟随多能细胞标记的获得。明显的慢病毒载体沉默是成功重编程hiPSC克隆的特征，但缺乏完全沉默并不妨碍hiPSC的诱导，维持或定向分化。此处描述的向量系统为重编程和hiPSC生成优化的机理研究提供了强大的工具。

著录项

  • 来源
  • 作者

    Eirini P. Papapetrou; Mark J. Tomishima; Stuart M. Chambers; Yvonne Mica; Evan Reed; Jayanthi Menon; Viviane Tabar; Qianxing Mo; Lorenz Studer; Michel Sadelain;

  • 作者单位

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Developmental Biology Programs, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 SKI Stem Cell Research Facility, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Developmental Biology Programs, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Gerstner Sloan-Kettering Graduate School, and Departments of Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Developmental Biology Programs, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

    Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065 Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, 10065;

  • 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

    fluorescent proteins; lentiviral vectors; silencing; stoichiometry;

    机译：荧光蛋白慢病毒载体;沉默化学计量;

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