...
  • 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 >Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules
【24h】

Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules

机译：揭示多能干细胞存活和小分子自我更新的核心信号调节机制

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

Using a high-throughput chemical screen, we identified two small molecules that enhance the survival of human embryonic stem cells (hESCs). By characterizing their mechanisms of action, we discovered an essential role of E-cadherin signaling for ESC survival. Specifically, we showed that the primary cause of hESC death following enzymatic dissociation comes from an irreparable disruption of E-cadherin signaling, which then leads to a fatal perturbation of integrin signaling. Furthermore, we found that stability of E-cadherin and the resulting survival of ESCs were controlled by specific growth factor signaling. Finally, we generated mESC-like hESCs by culturing them in mESC conditions. And these converted hESCs rely more on E-cadherin signaling and significantly less on integrin signaling. Our data suggest that differential usage of cell adhesion systems by ESCs to maintain self-renewal may explain their profound differences in terms of morphology, growth factor requirement, and sensitivity to enzymatic cell dissociation.
机译：使用高通量化学筛选，我们确定了两个小分子，它们增强了人类胚胎干细胞（hESCs）的存活率。通过表征其作用机制，我们发现了E-钙粘蛋白信号传导对ESC生存的重要作用。具体而言，我们表明酶解离后hESC死亡的主要原因来自E-钙粘蛋白信号传导的不可修复的破坏，然后导致整联蛋白信号传导的致命扰动。此外，我们发现E-钙粘着蛋白的稳定性和由此产生的ESC的生存受到特定生长因子信号的控制。最后，我们通过在mESC条件下培养它们来生成mESC样的hESC。这些转化的hESCs更多地依赖于E-钙粘蛋白信号传导，而更少地依赖于整联蛋白信号传导。我们的数据表明，ESC维持自我更新对细胞粘附系统的不同使用可能解释了它们在形态，生长因子要求和对酶促细胞解离的敏感性方面的深刻差异。

著录项

  • 来源
  • 作者

    Yue Xu; Xiuwen Zhu; Heung Sik Hahm; Wanguo Wei; Ergeng Hao; Alberto Hayek; Sheng Ding;

  • 作者单位

    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

    rnDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

    rnDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

    rnDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

    rnPediatric Research Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093;

    rnPediatric Research Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093;

    rnDepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;

  • 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

    human embryonic stem cell survival; cell-cell adhesion; cell-ECM adhesion;

    机译：人类胚胎干细胞存活;细胞间粘附;细胞-ECM粘附;

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