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Integrated spatial genomics reveals global architecture of single nuclei

Author

Listed:
  • Yodai Takei

    (California Institute of Technology)

  • Jina Yun

    (California Institute of Technology)

  • Shiwei Zheng

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health
    Icahn School of Medicine at Mount Sinai)

  • Noah Ollikainen

    (California Institute of Technology)

  • Nico Pierson

    (California Institute of Technology)

  • Jonathan White

    (California Institute of Technology)

  • Sheel Shah

    (California Institute of Technology)

  • Julian Thomassie

    (California Institute of Technology)

  • Shengbao Suo

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health
    Icahn School of Medicine at Mount Sinai)

  • Chee-Huat Linus Eng

    (California Institute of Technology)

  • Mitchell Guttman

    (California Institute of Technology)

  • Guo-Cheng Yuan

    (Dana-Farber Cancer Institute and Harvard T.H.Chan School of Public Health
    Icahn School of Medicine at Mount Sinai)

  • Long Cai

    (California Institute of Technology)

Abstract

Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies1–4. 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.

Suggested Citation

  • 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 , 2021. "Integrated spatial genomics reveals global architecture of single nuclei," Nature, Nature, vol. 590(7845), pages 344-350, February.
    • Handle: RePEc:nat:nature:v:590:y:2021:i:7845:d:10.1038_s41586-020-03126-2
    DOI: 10.1038/s41586-020-03126-2
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    Citations

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    Cited by:

    1. Kosuke Tomimatsu & Takeru Fujii & Ryoma Bise & Kazufumi Hosoda & Yosuke Taniguchi & Hiroshi Ochiai & Hiroaki Ohishi & Kanta Ando & Ryoma Minami & Kaori Tanaka & Taro Tachibana & Seiichi Mori & Akihito, 2024. "Precise immunofluorescence canceling for highly multiplexed imaging to capture specific cell states," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Jinhyun Kim & Sungsik Kim & Huiran Yeom & Seo Woo Song & Kyoungseob Shin & Sangwook Bae & Han Suk Ryu & Ji Young Kim & Ahyoun Choi & Sumin Lee & Taehoon Ryu & Yeongjae Choi & Hamin Kim & Okju Kim & Yu, 2023. "Barcoded multiple displacement amplification for high coverage sequencing in spatial genomics," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Xinyu Hu & Bob van Sluijs & Óscar García-Blay & Yury Stepanov & Koen Rietrae & Wilhelm T. S. Huck & Maike M. K. Hansen, 2024. "ARTseq-FISH reveals position-dependent differences in gene expression of micropatterned mESCs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Yingfeng Tao & Xiaoliu Zhou & Leqiang Sun & Da Lin & Huaiyuan Cai & Xi Chen & Wei Zhou & Bing Yang & Zhe Hu & Jing Yu & Jing Zhang & Xiaoqing Yang & Fang Yang & Bang Shen & Wenbao Qi & Zhenfang Fu & J, 2023. "Highly efficient and robust π-FISH rainbow for multiplexed in situ detection of diverse biomolecules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Bohan Li & Feng Bao & Yimin Hou & Fengji Li & Hongjue Li & Yue Deng & Qionghai Dai, 2024. "Tissue characterization at an enhanced resolution across spatial omics platforms with deep generative model," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    6. Ana Mota & Szymon Berezicki & Erik Wernersson & Luuk Harbers & Xiaoze Li-Wang & Katarina Gradin & Christiane Peuckert & Nicola Crosetto & Magda Bienko, 2022. "FRET-FISH probes chromatin compaction at individual genomic loci in single cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Robin Aguilar & Conor K. Camplisson & Qiaoyi Lin & Karen H. Miga & William S. Noble & Brian J. Beliveau, 2024. "Tigerfish designs oligonucleotide-based in situ hybridization probes targeting intervals of highly repetitive DNA at the scale of genomes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Halima H. Schede & Pradeep Natarajan & Arup K. Chakraborty & Krishna Shrinivas, 2023. "A model for organization and regulation of nuclear condensates by gene activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Lindsay Lee & Hongyu Yu & Bojing Blair Jia & Adam Jussila & Chenxu Zhu & Jiawen Chen & Liangqi Xie & Antonina Hafner & Shreya Mishra & Duan Dennis Wang & Caterina Strambio-De-Castillia & Alistair Boet, 2023. "SnapFISH: a computational pipeline to identify chromatin loops from multiplexed DNA FISH data," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    10. Michal Polonsky & Louisa M. S. Gerhardt & Jina Yun & Kari Koppitch & Katsuya Lex Colón & Henry Amrhein & Barbara Wold & Shiwei Zheng & Guo-Cheng Yuan & Matt Thomson & Long Cai & Andrew P. McMahon, 2024. "Spatial transcriptomics defines injury specific microenvironments and cellular interactions in kidney regeneration and disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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