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人类基因组中基本基因的识别和表征

Tim Wang¹, Kıvanç Birsoy¹, Nicholas W Hughes²

¹Department of Biology, Massachusetts Institute of Technology, Cambridge MA 02139, USA. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. David H. Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.

Science (New York, N.Y.)

|October 17, 2015

概括

通过CRISPR查发现了癌细胞生存和增殖的重要基因. 这些屏幕揭示了基本路径,未表征的RNA处理基因和细胞特异性,为癌症细胞责任性识别提供了战略.

科学领域:

基因组学
分子生物学
癌症研究

背景情况:

对致命表型的大规模遗传分析揭示了生物过程的分子基础.
细菌聚类定期间隔的短平行列重复 (CRISPR) 系统为基因查提供了强大的工具.

研究的目的:

通过全基因组CRISPR选,识别人类癌细胞增殖和生存所必需的基因.
通过正交方法验证发现并比较不同癌细胞系的基本基因组.
发现涉及至关重要的细胞过程中未经表征的基因,

主要方法:

为CRISPR查构建全基因组单导 RNA库.
在人类癌细胞系中选繁殖和生存所需的基因.
使用基于基因陷的直角选和与酵母基因淘汰的比较进行验证.
在多种癌细胞系中对CRISPR查进行比较分析.

主要成果:

鉴定了一组细胞必需基因的核心组件,这些基因富含基本路径的组成部分,高度表达的基因,以及具有很少失活多态的基因.
发现了一大批参与RNA处理的未表征的基因,其中一些基因定位在细胞核中.
细胞系间高基因重叠的证明,以及反映癌症类型和细胞特征的细胞特异性.

结论:

基于CRISPR的镜对于识别癌细胞中必不可少的基因具有强大作用.
已识别的基本基因提供了基本细胞通路和潜在的癌症负债的洞察力.
细胞特异性基因的重要性凸显了癌症的异质性和需要量身定制的治疗策略.

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