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多种表观遗传蛋白和基因转录的单细胞联合分析
Haiqing Xiong1, Qianhao Wang2, Chen C Li2
1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Science advances
|January 3, 2024
概括
我们开发了uCoTarget和uCoTargetX,用于超高通量单细胞表观基因组和转录基因组分析. 这些方法揭示了在造血干细胞/原始细胞分化过程中的关键表观遗传变化.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 单细胞生物学 单细胞生物学
- 分子生物学分子生物学
背景情况:
- 表观遗传修饰和转录因子结合调节基因表达和细胞命运.
- 目前的方法缺乏全面的多模式单细胞表观基因组分析的吞吐量.
研究的目的:
- 开发一种新的超高通量方法,用于单细胞中多个表观遗传标记的联合分析.
- 应用这种方法来研究在造血干细胞/原始细胞分化过程中的表观遗传动力学.
- 扩大用于同时转录组和表观基因组分析的方法.
主要方法:
- 开发uCoTarget,一个分组池条形码策略,用于单细胞多表观遗传分析.
- 优化灵敏度和分辨率,以检测五种基因素修饰 (H3K27ac,H3K4me3,H3K4me1,H3K36me3,H3K27me3) 的情况.
- 适用于血液构造干细胞/原始细胞 (HSPC) 的体外分化,并开发uCoTargetX用于转录组合.
主要成果:
- 使用uCoTarget在19,860个单细胞中同时检测了五种组素修饰.
- 在HSPC生成期间,在26418个单细胞中分析了多模式表观基因组概况.
- 在HSPC分化过程中识别增强剂-促进剂配对 (H3K27ac,H3K4me3) 和RUNX1参与.
结论:
- uCoTarget和uCoTargetX为多式单细胞表观基因组和转录基因组分析提供了多功能,可通用的工具.
- 这些方法可以重建表观基因组和转录基因组景观.
- 促进了在细胞命运规范过程中单细胞水平的调控相互作用的分析.
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