在T辅助细胞中的全基因组CRISPR屏幕揭示了激活和分化之间的普遍交叉声
Johan Henriksson1, Xi Chen2, Tomás Gomes2
1Wellcome Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK; Department of Biosciences and Nutrition, Karolinska Institutet, Hälsovägen 7, Novum, SE-141 83, Huddinge, Sweden.
Cell
|January 15, 2019
概括
研究人员绘制了控制T助手2型 (Th2) 细胞激活和分化的基因网络. 这项研究揭示了适应性免疫,自身免疫和癌症免疫学的关键调节者.
科学领域:
- 免疫学
- 分子生物学
- 遗传学
背景情况:
- 2型T辅助细胞 (Th2) 是适应性免疫的关键调节者.
- Th2细胞在感染,自身免疫和瘤免疫学中起作用.
研究的目的:
- 解剖 Th2 细胞激活和分化的调节电路.
- 区分和定量分析细胞激活与分化过程.
主要方法:
- 使用全基因组的逆转录病毒CRISPR淘汰库.
- 综合RNA-seq,ATAC-seq和ChIP-seq进行综合分析.
- 结合生化和遗传数据创建一个监管图谱.
主要成果:
- 证明Th2细胞激活和分化是紧密相关的过程.
- 确定了许多转录因子,代谢基因和细胞因子/受体对共同控制这些过程.
- 在没有影响激活的情况下,发现了一组专门调节差异化的基因.
结论:
- 提供了Th2细胞分化的详细地图,验证已知的调节剂.
- 确定了新的核心监管网络组件,包括Pparg和Bhlhe40.
- 阐明了控制Th2辅助细胞命运的复杂调节机制.
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