通过单细胞微球菌核酶测序揭示的核体组织原理
Binbin Lai1, Weiwu Gao1,2, Kairong Cui1
1Laboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
Nature
|September 28, 2018
概括
单细胞微球菌核酶测序 (scMNase-seq) 揭示了细胞对细胞的核素定位和染色质可访问性. 这种新方法揭示了与基因活动和细胞分化潜力相关的核细胞组织原理.
科学领域:
- 基因组学
- 表观遗传学
- 细胞生物学
背景情况:
- 核细胞的定位会影响染色体的可访问性和基因表达.
- 现有的方法提供细胞平均核形状,掩盖细胞异质性.
- 基因表达的细胞异质性可能源于染色体可访问性的变化.
研究的目的:
- 在单个细胞中开发和应用一种用于同时测定全基因组核细胞定位和染色质可访问性的新技术.
- 研究核细胞组织的原理及其与基因活动和细胞状态的关系.
- 在不同类型的细胞中探索细胞对细胞的染色体组织变化.
主要方法:
- 开发单细胞微核酶测序 (scMNase-seq).
- 将scMNase-seq应用于NIH3T3细胞,小鼠原始的CD4T细胞和小鼠胚胎干细胞.
- 在单细胞分辨率下对全基因组核细胞定位和染色质可访问性的分析.
主要成果:
- scMNase-seq揭示了两个不同的核细胞组织原理:静态/异染色体区域的均间距高位变异,以及低位变异的活性基因/DNase I过敏区域的异质间距.
- 在DNase I过敏位点的核细胞间距的双模分布与可访问性状态和细胞间变异相关.
- 单个细胞内的核细胞变异低于跨细胞的变异,而同一个细胞类型内的变异低于跨细胞类型的变异.
- 不分化的细胞在基因系特异增强剂中显示核细胞占用量减少,这表明分化的原始化.
结论:
- scMNase-seq提供了前所未有的关于单细胞核细胞组织和染色体可访问性的洞察力.
- 核位表现出细胞类型和基因活动相关的异质性.
- 这些发现显示了基于染色体可访问性模式的干细胞和T细胞的预先分化状态.
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