Spatially resolved single-cell genomics and transcriptomics by imaging

The recent advent of genome-scale imaging has enabled single-cell omics analysis in a spatially resolved manner in intact cells and tissues. These advances allow gene expression profiling of individual cells, and hence in situ identification and spatial mapping of cell types, in complex tissues. The high spatial resolution of these approaches further allows determination of the spatial organizations of the genome and transcriptome inside cells, both of which are key regulatory mechanisms for gene expression.

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Fig. 1: Imaging-based single cell genomics and transcriptomics approaches.
Fig. 2: Three example application areas of imaging-based single-cell genomics and transcriptomics.

References

  1. 1.

    Larsson, L., Frisén, J. & Lundeberg, J. Nat. Methods https://doi.org/10.1038/s41592-020-01038-7 (2021).

  2. 2.

    Femino, A. M., Fay, F. S., Fogarty, K. & Singer, R. H. Science 280, 585–590 (1998).

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Raj, A., van den Bogaard, P., Rifkin, S. A., van Oudenaarden, A. & Tyagi, S. Nat. Methods 5, 877–879 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Levsky, J. M., Shenoy, S. M., Pezo, R. C. & Singer, R. H. Science 297, 836–840 (2002).

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. Science 348, aaa6090 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  6. 6.

    Xia, C., Fan, J., Emanuel, G., Hao, J. & Zhuang, X. Proc. Natl Acad. Sci. USA 116, 19490–19499 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Chen, F., Tillberg, P. W. & Boyden, E. S. Science 347, 543–548 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Wang, G., Moffitt, J. R. & Zhuang, X. Sci. Rep. 8, 4847 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  9. 9.

    Moffitt, J. R. et al. Proc. Natl Acad. Sci. USA 113, 14456–14461 (2016).

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Moffitt, J. R. et al. Science 362, eaau5324 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  11. 11.

    Su, J. H., Zheng, P., Kinrot, S. S., Bintu, B. & Zhuang, X. Cell 182, 1641–1659.e26 (2020).

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Lubeck, E., Coskun, A. F., Zhiyentayev, T., Ahmad, M. & Cai, L. Nat. Methods 11, 360–361 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Shah, S., Lubeck, E., Zhou, W. & Cai, L. Neuron 92, 342–357 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Eng, C. L. et al. Nature 568, 235–239 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Codeluppi, S. et al. Nat. Methods 15, 932–935 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Beliveau, B. J. et al. Proc. Natl Acad. Sci. USA 109, 21301–21306 (2012).

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Xia, C., Babcock, H. P., Moffitt, J. R. & Zhuang, X. Sci. Rep. 9, 7721 (2019).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. 18.

    Landegren, U. BioEssays 15, 761–765 (1993).

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Goh, J. J. L. et al. Nat. Methods 17, 689–693 (2020).

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Ke, R. et al. Nat. Methods 10, 857–860 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Wang, X. et al. Science 361, eaat5691 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  22. 22.

    Qian, X. et al. Nat. Methods 17, 101–106 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Iyer, E.P.R. et al. Preprint at bioRxiv https://doi.org/10.1101/281121 (2018).

  24. 24.

    Alon, S. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.05.13.094268 (2020).

  25. 25.

    Chen, X., Sun, Y. C., Church, G. M., Lee, J. H. & Zador, A. M. Nucleic Acids Res. 46, e22 (2018).

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Lee, J. H. et al. Science 343, 1360–1363 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Stuart, T. et al. Cell 177, 1888–1902.e21 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Biancalani, T. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.08.29.272831 (2020).

  29. 29.

    Zhang, M. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.06.04.105700 (2020).

  30. 30.

    Chen, W. T. et al. Cell 182, 976–991.e19 (2020).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Asp, M. et al. Cell 179, 1647–1660.e19 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Soldatov, R. et al. Science 364, eaas9536 (2019).

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Moffitt, J. R. et al. Proc. Natl Acad. Sci. USA 113, 11046–11051 (2016).

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Wang, G. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.12.07.414060 (2020).

  35. 35.

    Wang, S. et al. Science 353, 598–602 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Nguyen, H. Q. et al. Nat. Methods 17, 822–832 (2020).

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Bintu, B. et al. Science 362, eaau1783 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  38. 38.

    Nir, G. et al. PLoS Genet. 14, e1007872 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  39. 39.

    Mateo, L. J. et al. Nature 568, 49–54 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Cardozo Gizzi, A. M. et al. Mol. Cell 74, 212–222.e5 (2019).

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Sawh, A. N. et al. Mol. Cell 78, 96–111.e6 (2020).

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Liu, M. et al. Nat. Commun. 11, 2907 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Takei, Y. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.11.29.403055 (2020).

  44. 44.

    Lawson, M. J. et al. Mol. Syst. Biol. 13, 947 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  45. 45.

    Emanuel, G., Moffitt, J. R. & Zhuang, X. Nat. Methods 14, 1159–1162 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Wang, C., Lu, T., Emanuel, G., Babcock, H. P. & Zhuang, X. Proc. Natl Acad. Sci. USA 116, 10842–10851 (2019).

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Feldman, D. et al. Cell 179, 787–799.e17 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Camsund, D. et al. Nat. Methods 17, 86–92 (2020).

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Frieda, K. L. et al. Nature 541, 107–111 (2017).

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Chow, K.-H. K. et al. Preprint at bioRxiv https://doi.org/10.1101/2020.02.21.958678 (2020).

  51. 51.

    Chen, X. et al. Cell 179, 772–786.e19 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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Acknowledgements

I am grateful to J. Moffitt for suggestions and comments on the paper, and to J. Moffitt, B. Bintu and J. Fan for help with figures. This work is supported in part by the National Institutes of Health. X.Z. is a Howard Hughes Medical Institute investigator.

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Correspondence to Xiaowei Zhuang.

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X.Z. is a cofounder and consultant of Vizgen and an inventor on patents applied for by Harvard University related to MERFISH.

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Zhuang, X. Spatially resolved single-cell genomics and transcriptomics by imaging. Nat Methods 18, 18–22 (2021). https://doi.org/10.1038/s41592-020-01037-8

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