• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >A reversible haploid mouse embryonic stem cell biobank resource for functional genomics
【24h】

A reversible haploid mouse embryonic stem cell biobank resource for functional genomics

机译：功能基因组学的可逆单倍体小鼠胚胎干细胞生物库资源

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

The ability to directly uncover the contributions of genes to a given phenotype is fundamental for biology research. However, ostensibly homogeneous cell populations exhibit large clonal variance(1,2) that can confound analyses and undermine reproducibility(3). Here we used genome-saturated mutagenesis to create a biobank of over 100,000 individual haploid mouse embryonic stem (mES) cell lines targeting 16,970 genes with genetically barcoded, conditional and reversible mutations. This Haplobank is, to our knowledge, the largest resource of hemi/homozygous mutant mES cells to date and is available to all researchers. Reversible mutagenesis overcomes clonal variance by permitting functional annotation of the genome directly in sister cells. We use the Haplobank in reverse genetic screens to investigate the temporal resolution of essential genes in mES cells, and to identify novel genes that control sprouting angiogenesis and lineage specification of blood vessels. Furthermore, a genome-wide forward screen with Haplobank identified PLA2G16 as a host factor that is required for cytotoxicity by rhinoviruses, which cause the common cold. Therefore, clones from the Haplobank combined with the use of reversible technologies enable high-throughput, reproducible, functional annotation of the genome.
机译：直接发现基因对给定表型的贡献的能力是生物学研究的基础。然而，表面上均质的细胞群体表现出较大的克隆变异性（1,2），这会混淆分析并破坏重现性（3）。在这里，我们使用基因组饱和诱变技术创建了超过100,000个单个单倍体小鼠胚胎干（mES）细胞系的生物库，这些细胞系针对具有遗传条形码，条件性和可逆突变的16,970个基因。据我们所知，Haplobank是迄今为止最大的半/纯合突变mES细胞资源，可供所有研究人员使用。可逆诱变通过允许直接在姐妹细胞中对基因组进行功能注释来克服克隆变异。我们在逆向遗传筛选中使用Haplobank来研究mES细胞中必需基因的时间分辨率，并确定控制发芽血管生成和血管谱系规范的新基因。此外，用Haplobank进行的全基因组正向筛选将PLA2G16鉴定为鼻病毒引起细胞毒性所需的宿主因子，这可引起普通感冒。因此，来自Haplobank的克隆结合可逆技术的使用可实现基因组的高通量，可重现，功能性注释。

著录项

  • 来源
    《Nature》 |2017年第7674期|114-118|共5页
  • 作者

    Elling Ulrich; Wimmer Reiner A.; Leibbrandt Andreas; Urkard Thomas B.; Michlits Georg; Leopoldi Alexandra; Micheler Thomas; Abdeen Dana; Zhuk Sergei; Aspalter Irene M.; Handl Cornelia; Liebergesell Julia; Hubmann Maria; Husa Anna-Maria; Kinzer Manuela; Schuller Nicole; Wetzel Ellen; van de Loo Nina; Zepeda Martinez Jorge Arturo; Estoppey David; Riedl Ralph; Yang Fengtang; Fu Beiyuan; Dechat Thomas; Ivics Zoltan; Agu Chukwuma A.; Bell Oliver; Blaas Dieter; Gerhardt Holger; Hoepfner Dominic; Stark Alexander; Penninger Josef M.;

  • 作者单位

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Vienna Bioctr VBC, Vienna Bioctr Core Facil, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    UCL, MRC Lab Mol Cell Biol, London, England|UCL, Inst Phys Living Syst, London, England;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Novartis Inst BioMed Res, Basel, Switzerland;

    Novartis Inst BioMed Res, Basel, Switzerland;

    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England;

    Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England;

    Med Univ Vienna, Max F Perutz Labs, Dr Bohr Gasse 9, Vienna, Austria;

    Paul Ehrlich Inst, Paul Ehrlich Str 51-59, D-63225 Langen, Germany;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

    Med Univ Vienna, Max F Perutz Labs, Dr Bohr Gasse 9, Vienna, Austria;

    Helmholtz Assoc, Max Delbruck Ctr Mol Med, Berlin, Germany|German Ctr Cardiovasc Res, Berlin, Germany|Berlin Inst Hlth, Berlin, Germany;

    Novartis Inst BioMed Res, Basel, Switzerland;

    Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Dr Bohr Gasse 7, A-1030 Vienna, Austria;

    Austrian Acad Sci IMBA, Inst Mol Biotechnol, Vienna Bioctr VBC, Dr Bohr Gasse 3, Vienna, Austria;

  • 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