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Integrated spatial genomics reveals global architecture of single nuclei

机译:综合空间基因组学揭示了单一核的全球结构

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Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies~(1-4). Because individual cells appear to be highly variable at all these levels~(5), 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.
机译:鉴定染色体结构,核体,染色质态和基因表达之间的关系是核组织研究的总体目标〜(1-4)。由于各个细胞在所有这些级别似乎是高度变化的〜(5),因此必须在同一单元格中映射不同的模态。在这里,我们使用DNA Seqfish +在单小鼠胚胎茎(ES)细胞中的3,660个染色体基因座的成像,以及通过顺序免疫荧光和70RNA的表达曲线和70RNA的表达谱系和亚核结构。许多基因座总是与单小鼠ES细胞中免疫荧光标记相关的。这些基因座在单细胞的核组织中“固定点”,通常出现在核体和组合染色质标记所定义的区域的表面上。此外,高表达的基因似乎预先定位到活性核区域,与单细胞中的突发动力学无关。我们的分析还发现了具有特征组合染色质态的几种不同的小鼠ES细胞亚群。利用克隆分析,我们表明一些染色质标记的全球水平,例如赖氨酸27(H3K27ME3)和MAMROH2A1(MH2A1)的H3三甲基化,在至少3-4代中是可遗传的,而其他标记在更快的时间尺度上波动。该SEQFISH +基于空间多模式方法可用于探索各种生物系统中的核组织和细胞状态。

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  • 来源
    《Nature》 |2021年第7845期|344-350|共7页
  • 作者单位

    Division of Biology and Biological Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health|Department of Genetics and Genomic Sciences and Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai;

    Division of Biology and Biological Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health|Department of Genetics and Genomic Sciences and Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai;

    Division of Chemistry and Chemical Engineering California Institute of Technology;

    Division of Biology and Biological Engineering California Institute of Technology;

    Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health|Department of Genetics and Genomic Sciences and Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai;

    Division of Biology and Biological Engineering California Institute of Technology;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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