美国加州理工学院的蔡龙研究团队取得一项新成果。他们利用整合的空间基因组学揭示了单核的整体架构。2021年1月27 日的国际知名学术期刊《自然》杂志发表了这一成果。
他们报告了使用DNA seqFISH +在单个小鼠胚胎干（ES）细胞中对3,660个染色体基因座的成像，以及通过序列免疫荧光和70个RNA的表达谱，以及17个染色质标记和亚核结构。在单个小鼠ES细胞中，许多基因座总是与免疫荧光标记相关。这些基因座在单个细胞的核组织中形成“固定点”，并频繁出现在核染色质标记定义的核体和区域表面上。
此外，高表达基因似乎被预先定位在活性核区，而与单个细胞的爆发动力学无关。他们的分析还发现了具有特征性组合染色质状态的几个不同的小鼠ES细胞亚群。使用克隆分析，他们显示了某些染色质标记的总体水平，例如赖氨酸27（H3K27me3）和macroH2A1（mH2A1）的H3三甲基化，至少可遗传3到4代，而其他标记则在更快的时间范围内波动。这种基于seqFISH +的空间多峰方法可用于探索多种生物系统中的核组织和细胞状态。
据介绍，鉴定染色体结、核体、染色质状态与基因表达之间的关系是核组织研究的首要目标。由于单个细胞在所有这些水平上似乎都高度可变，因此必须在同一细胞中绘制不同的模式。
附：英文原文
Title: Integrated spatial genomics reveals global architecture of single nuclei
Author: Yodai Takei, Jina Yun, Shiwei Zheng, Noah Ollikainen, Nico Pierson, Jonathan White, Sheel Shah, Julian Thomassie, Shengbao Suo, Chee-Huat Linus Eng, Mitchell Guttman, Guo-Cheng Yuan, Long Cai
Issue&Volume: 2021-01-27
Abstract: Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies1,2,3,4. Because individual cells appear to be highly variable at all these levels5, it is essential to map different modalities in the same cells. Here we report the imaging of 3,660 chromosomal loci in single mouse embryonic stem (ES) cells using DNA seqFISH+, along with 17 chromatin marks and subnuclear structures by sequential immunofluorescence and the expression profile of 70 RNAs. Many loci were invariably associated with immunofluorescence marks in single mouse ES cells. These loci form ‘fixed points’ in the nuclear organizations of single cells and often appear on the surfaces of nuclear bodies and zones defined by combinatorial chromatin marks. Furthermore, highly expressed genes appear to be pre-positioned to active nuclear zones, independent of bursting dynamics in single cells. Our analysis also uncovered several distinct mouse ES cell subpopulations with characteristic combinatorial chromatin states. Using clonal analysis, we show that the global levels of some chromatin marks, such as H3 trimethylation at lysine 27 (H3K27me3) and macroH2A1 (mH2A1), are heritable over at least 3–4 generations, whereas other marks fluctuate on a faster time scale. This seqFISH+-based spatial multimodal approach can be used to explore nuclear organization and cell states in diverse biological systems.
DOI: 10.1038/s41586-020-03126-2
Source: https://www.nature.com/articles/s41586-020-03126-2
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
