Integrated spatial genomics reveals global architecture of single nuclei.
Integrated spatial genomics reveals global architecture of single nuclei.
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整合空间基因组学揭示了单核的全球架构。
DOI：
10.1038/s41586-020-03126-2
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发表时间：
2021-03
期刊：
影响因子：
64.8
通讯作者：
Cai L
中科院分区：
文献类型：
--
作者：
Takei Y;Yun J;Zheng S;Ollikainen N;Pierson N;White J;Shah S;Thomassie J;Suo S;Eng CL;Guttman M;Yuan GC;Cai L
确定染色体结构，核体，染色质状态和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，因此必须在相同细胞中映射不同的模式。在这里，我们报告了3，660个染色体位点在单个小鼠胚胎干细胞（mESCs）的DNA seqFISH+，沿着17个染色质标记和亚核结构的顺序免疫荧光（IF）和70 RNA的表达谱成像。我们发现在单个mESC中，许多位点与IF标记恒定相关。这些位点在单个细胞的核组织中形成“固定点”，并且经常出现在核体的表面和由组合染色质标记限定的区域上。此外，高表达的基因似乎被预先定位到活跃的核区，独立于单细胞中的爆发动力学。我们的分析还发现了几个不同的mESCs亚群的特征组合染色质状态。使用克隆分析，我们表明，全球水平的一些染色质标记，如H3 K27 me 3和macroH 2A 1（mH 2A 1），是可遗传的至少3-4代，而其他标记波动更快的时间尺度。这种基于seqFISH+的空间多模态方法可用于探索不同生物系统中的核组织和细胞状态。
Identifying the relationships between chromosome structures, nuclear bodies, chromatin states, and gene expression is an overarching goal of nuclear organization studies. Because individual cells appear to be highly variable at all these levels, 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 cells (mESCs) by DNA seqFISH+, along with 17 chromatin marks and subnuclear structures by sequential immunofluorescence (IF) and the expression profile of 70 RNAs. We found many loci were invariantly associated with IF marks in single mESCs. These loci form “fixed points” in the nuclear organizations in 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 mESCs subpopulations with characteristic combinatorial chromatin states. Using clonal analysis, we show that the global levels of some chromatin marks, such as 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.
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影响因子：
4.9
作者：
Bao W;Kojima KK;Kohany O
通讯作者：
Kohany O
DOI：
10.1083/jcb.145.6.1119
发表时间：
1999-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Croft JA;Bridger JM;Boyle S;Perry P;Teague P;Bickmore WA
通讯作者：
Bickmore WA
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian
影响因子：
64.5
作者：
Bonev B;Mendelson Cohen N;Szabo Q;Fritsch L;Papadopoulos GL;Lubling Y;Xu X;Lv X;Hugnot JP;Tanay A;Cavalli G
通讯作者：
Cavalli G