首页> 外文期刊>Genes & Development >Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal
【24h】

Sox17 promotes differentiation in mouse embryonic stem cells by directly regulating extraembryonic gene expression and indirectly antagonizing self-renewal

机译:Sox17通过直接调节胚外基因表达并间接拮抗自我更新来促进小鼠胚胎干细胞的分化

获取原文
获取原文并翻译 | 示例

摘要

In embryonic stem (ES) cells, a well-characterized transcriptional network promotes pluripotency and represses gene expression required for differentiation. In comparison, the transcriptional networks that promote differentiation of ES cells and the blastocyst inner cell mass are poorly understood. Here, we show that Sox17 is a transcriptional regulator of differentiation in these pluripotent cells. ES cells deficient in Sox17 fail to differentiate into extraembryonic cell types and maintain expression of pluripotency-associated transcription factors, including Oct4, Nanog, and Sox2. In contrast, forced expression of Sox17 down-regulates ES cell-associated gene expression and directly activates genes functioning in differentiation toward an extraembryonic endoderm cell fate. We show these effects of Sox17 on ES cell gene expression are mediated at least in part through a competition between Sox17 and Nanog for common DNA-binding sites. By elaborating the function of Sox17, our results provide insight into how the transcriptional network promoting ES cell self-renewal is interrupted, allowing cellular differentiation.
机译:在胚胎干(ES)细胞中,特征明确的转录网络可促进多能性并抑制分化所需的基因表达。相比之下,促进ES细胞分化和胚泡内部细胞团的转录网络知之甚少。在这里,我们显示Sox17是这些多能细胞中分化的转录调节因子。缺乏Sox17的ES细胞无法分化为胚外细胞类型,并且无法维持多能性相关转录因子的表达,包括Oct4,Nanog和Sox2。相反,Sox17的强迫表达下调了ES细胞相关基因的表达,并直接激活了分化为胚外内胚层细胞命运的基因。我们显示Sox17对ES细胞基因表达的这些影响至少部分地通过Sox17与Nanog之间对于常见DNA结合位点的竞争而介导。通过阐述Sox17的功能,我们的结果提供了关于促进ES细胞自我更新的转录网络如何被中断,允许细胞分化的见解。

著录项

  • 来源
    《Genes & Development》 |2010年第3期|312-326|共15页
  • 作者单位

    Stowers Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA;

    Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Stowers Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massacusetts 02138, USA;

    Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Stowers Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Stowers Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

    Stowers Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138, USA|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massacusetts 02138, USA|Harvard Stem Cell Institute, Harvard University, Cambridge, Massacusetts 02138, USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Differentiation; self-renewal; transcriptional network; primitive endoderm; stem cell; Sox17;

    机译:分化;自我更新;转录网络;原始内胚层;干细胞;Sox17;

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