多基因组 Perturb-seq 解锁了对转录基因组和表观基因组集成扰动效应的可扩展发现
Eli Metzner1,2, Kaden M Southard1, Thomas M Norman1
1Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
这项研究引入了Multiome Perturb-seq,这是一种将遗传变化与基因表达和染色体可访问性联系起来的新方法. 这种技术有助于揭示细胞状态变化的调控基础,推进遗传查能力.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 单细胞CRISPR屏幕将遗传干扰与转录状态联系起来.
- 连接诱导遗传变化的高通量方法与它们的监管基础是有限的.
研究的目的:
- 介绍Multiome Perturb-seq,一种扩展单细胞CRISPR屏幕的方法,同时测量基因表达和染色质可访问性变化.
- 通过分析扰动的综合效应,剖析支细胞状态的调节逻辑.
主要方法:
- 在CRISPR干扰 (CRISPRi) 屏幕中,在人类RPE-1细胞中应用了13种染色体重塑剂的多细胞乱-seq.
- 利用一种改进的方法来捕获核RNA的条形码转录,以有效地分配sgRNA的身份.
- 组织表达和可访问性测量到连贯的程序中.
主要成果:
- 成功地将基因表达中的扰动诱导的变化与单细胞水平上的染色质可访问性联系起来.
- 确定ARID1A和SUZ12的淘汰会诱导对发育特征进行丰富的程序.
- 伪物质分析将染色质可访问性的变化与基因表达的改变联系起来.
结论:
- Multiome Perturb-seq提供了一个可扩展和简单实现的系统来剖析监管逻辑.
- 多模式分析对了解遗传干扰对细胞状态的综合影响很有价值.
- 该方法提升了将遗传干扰与其潜在的调节机制联系起来的能力.
关键词:
克里斯普里是指克里斯普里.这就是 Perturb-seqq.染色质可访问性 染色质可访问性功能性基因组学 功能性基因组学基因监管网络 基因监管网络它们是多原子的.单细胞基因组学 单细胞基因组学更多相关视频
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