Nature:RNAi分析细胞分裂关键基因

【字体: 时间:2010年04月06日 来源:生物通

编辑推荐:

  英国Wellcome Trust研究所基因组研究中心,德国欧盟分子生物实验室等多个科研机构的科学家通过系统基因组分析的方式找到影响细胞分裂的关键基因,相关成果文章Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes公布在最新一期的Nature上。

  

生物通报道,英国Wellcome Trust研究所基因组研究中心,德国欧盟分子生物实验室等多个科研机构的科学家通过系统基因组分析的方式找到影响细胞分裂的关键基因,相关成果文章Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes公布在最新一期的Nature上。

 

研究小组利用RNAi将人类细胞系中大约21,000个蛋白编码基因中的每个基因沉默,然后利用对活的、正在分裂的细胞进行高通过量时间延迟成像的方法来记录结果。通过对每个基因至少6个时长为两天的影片进行计算机图像处理,来对表现型进行量化打分。

 

数百个基因被发现在有丝分裂和包括细胞存活及迁移在内的其他细胞过程中发挥功能。该研究的整个数据集作为一个公共功能基因组资源发布在www.mitocheck.org这个网站上。有兴趣的读者不妨登陆查看。

 

细胞分裂(cell division)是活细胞繁殖其种类的过程,是一个细胞分裂为两个细胞的过程。分裂前的细胞称母细胞,分裂后形成的新细胞称子细胞。通常包括核分裂和胞质分裂两步。在核分裂过程中母细胞把遗传物质传给子细胞。在单细胞生物中细胞分裂就是个体的繁殖,在多细胞生物中细胞分裂是个体生长、发育和繁殖的基础。1855年德国学者魏尔肖(R.Virchow)提出“一切细胞来自细胞”的著名论断,即认为个体的所有细胞都是由原有细胞分裂产生的。现在除细胞分裂外还没有证据说明细胞繁殖有其他途经。

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Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes

Beate Neumann1,12, Thomas Walter1,12, Jean-Karim Hériché5,13, Jutta Bulkescher1, Holger Erfle1,3,13, Christian Conrad1,3, Phill Rogers1,13, Ina Poser6, Michael Held1,13, Urban Liebel1,13, Cihan Cetin3, Frank Sieckmann8, Gregoire Pau9, Rolf Kabbe10, Annelie Wünsche2, Venkata Satagopam4, Michael H. A. Schmitz7, Catherine Chapuis3, Daniel W. Gerlich7, Reinhard Schneider4, Roland Eils10, Wolfgang Huber9, Jan-Michael Peters11, Anthony A. Hyman6, Richard Durbin5, Rainer Pepperkok3 & Jan Ellenberg2

 

MitoCheck Project Group,

Gene Expression and,

Cell Biology/Biophysics Units, Structural and,

Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK

Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany

Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland

Leica Microsystems CMS GmbH, Am Friedensplatz 3, D-68165 Mannheim, Germany

European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge CB10 1SD, UK

Division of Theoretical Bioinformatics, German Cancer Research Center, Im Neuenheimer Feld 267, D-69120 Heidelberg, Germany

Institute for Molecular Pathology, Dr Bohr Gasse 7, A-1030 Vienna, Austria

These authors contributed equally to this work.

Present addresses: MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany (J.-K.H.); BIOQUANT Centre University Heidelberg, INF 267, D-69120 Heidelberg, Germany (H.E.); 3-V Biosciences GmbH, Wagistrasse 27, 8952 Schlieren, Switzerland (P.R.); Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland (M.H.); Karlsruhe Institute of Technology KIT, Herrmann-von-Helmholtz Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany (U.L.).

Correspondence to: Jan Ellenberg2 Correspondence and requests for materials should be addressed to J.E. (Email: jan.ellenberg@embl.de).

 

Abstract

Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the ~21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.

 

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