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一个全基因组的CRISPR屏幕在初级免疫细胞中解剖调节网络

Oren Parnas¹, Marko Jovanovic¹, Thomas M Eisenhaure²

¹Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

|July 21, 2015

概括

这项研究使用了树突细胞的CRISPR查来发现控制瘤亡因子 (Tnf) 对脂多糖 (LPS) 的反应的基因. 研究人员确定了已知的和新的调节剂,揭示了对天生的免疫细胞循环的新见解.

科学领域:

免疫学
细胞生物学
遗传学

背景情况:

解剖哺乳动物的细胞循环是一项挑战.
了解先天性免疫反应,比如通过TLR4诱导Tnf,对于宿主防御至关重要.

研究的目的:

通过全基因组选,在树突细胞中识别控制Tnf诱导的基因.
在先天免疫路径中对新发现的基因进行功能分类.

主要方法:

在树突细胞中进行全基因组CRISPR-Cas9库选.
通过测量蛋白质标记物和mRNA资料来验证候选基因.
基于LPS反应的基因功能分类.

主要成果:

确定了已知和数十种新型TLR4信号调节器.
验证了候选基因并将其分为三个功能模块.
在LPS反应中突出显示PAF和寡糖转移酶 (OST) 复合物的作用.

结论:

发现了天生的免疫电路中的新组件和功能.
提供了剖析哺乳动物细胞电路的遗传方法.
对细菌刺激的树突细胞反应的先进理解.

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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