Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Single-cell biology: beyond the sum of its parts

The field of single-cell RNA sequencing (scRNA-seq) has been paired with genomics, epigenomics, spatial omics, proteomics and imaging to achieve multimodal measurements of individual cellular phenotypes and genotypes. In its purest form, single-cell multimodal omics involves the simultaneous detection of multiple traits in the same cell. More broadly, multimodal omics also encompasses comparative pairing and computational integration of measurements made across multiple distinct cells to reconstruct phenotypes. Here I highlight some of the biological insights gained from multimodal studies and discuss the challenges and opportunities in this emerging field.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Plasschaert, L. W. et al. Nature 560, 377–381 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Montoro, D. T. et al. Nature 560, 319–324 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Nat. Biotechnol. 33, 495–502 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    McKenna, A. & Gagnon, J. A. Development 146, dev169730 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Baron, C. S. & van Oudenaarden, A. Nat. Rev. Mol. Cell Biol. 20, 753–765 (2019).

    CAS  PubMed  Google Scholar 

  6. 6.

    Suvà, M. L. & Tirosh, I. Mol. Cell 75, 7–12 (2019).

    PubMed  Google Scholar 

  7. 7.

    Nathan, A., Baglaenko, Y., Fonseka, C. Y., Beynor, J. I. & Raychaudhuri, S. Curr. Opin. Immunol. 61, 17–25 (2019).

    CAS  PubMed  Google Scholar 

  8. 8.

    Zeng, H. & Sanes, J. R. Nat. Rev. Neurosci. 18, 530–546 (2017).

    CAS  PubMed  Google Scholar 

  9. 9.

    Huang, Z. J. & Paul, A. Nat. Rev. Neurosci. 20, 563–572 (2019).

    CAS  PubMed  Google Scholar 

  10. 10.

    Gottgens, B. & Kucinski, I. in Stem Cells: From Biological Principles to Regenerative Medicine (eds. Lo Celso, C., Red-Horse, K. & Watt, F. M.) (Cold Spring Harbor Laboratory Press, 2019); https://doi.org/10.17863/CAM.44977.

  11. 11.

    Trapnell, C. et al. Nat. Biotechnol. 32, 381–386 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Bendall, S. C. et al. Cell 157, 714–725 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Farrell, J. A. et al. Science 360, eaar3131 (2018).

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Briggs, J. A. et al. Science 360, eaar5780 (2018).

    PubMed  PubMed Central  Google Scholar 

  15. 15.

    Wagner, D. E. et al. Science 360, 981–987 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Cao, J. et al. Nature 566, 496–502 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Pijuan-Sala, B. et al. Nature 566, 490–495 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

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

    CAS  PubMed  Google Scholar 

  19. 19.

    Packer, J. S. et al. Science 365, eaax1971 (2019).

    CAS  PubMed  Google Scholar 

  20. 20.

    Mizeracka, K., Rogers, J. M., Shaham, S., Bulyk, M. L. & Heiman, M. G. Preprint at https://doi.org/10.1101/758508 (2019).

  21. 21.

    Stubbington, M. J. T. et al. Nat. Methods 13, 329–332 (2016).

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    Lee-Six, H. et al. Nature 561, 473–478 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Ludwig, L. S. et al. Cell 176, 1325–1339.e22 (2019).

    CAS  PubMed  Google Scholar 

  24. 24.

    Sun, J. et al. Nature 514, 322–327 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Raj, B. et al. Nat. Biotechnol. 36, 442–450 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Lacin, H. et al. eLife 8, 1113 (2019).

    Google Scholar 

  27. 27.

    Doe, C. Q. Annu. Rev. Cell Dev. Biol. 33, 219–240 (2017).

    CAS  PubMed  Google Scholar 

  28. 28.

    He, J. et al. Neuron 75, 786–798 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sánchez-Guardado, L. & Lois, C. eLife 8, 766 (2019).

    Google Scholar 

  30. 30.

    Biddy, B. A. et al. Nature 564, 219–224 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Achim, K. et al. Nat. Biotechnol. 33, 503–509 (2015).

    CAS  PubMed  Google Scholar 

  32. 32.

    Lein, E., Borm, L. E. & Linnarsson, S. Science 358, 64–69 (2017).

    CAS  PubMed  Google Scholar 

  33. 33.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

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

    CAS  PubMed  Google Scholar 

  35. 35.

    Muñoz-Manchado, A. B. et al. Cell Reports 24, 2179–2190.e7 (2018).

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Gouwens, N. W. et al. Nat. Neurosci. 22, 1182–1195 (2019).

    CAS  PubMed  Google Scholar 

  37. 37.

    Li, H. et al. Cell 171, 1206–1220.e22 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

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

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kim, D.-W. et al. Cell 179, 713–728.e17 (2019).

    CAS  PubMed  Google Scholar 

  40. 40.

    van Galen, P. et al. Cell 176, 1265–1281.e24 (2019).

    PubMed  Google Scholar 

  41. 41.

    Cao, J. et al. Science 361, 1380–1385 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Argelaguet, R. et al. Nature https://doi.org/10.1038/s41586-019-1825-8 (2019).

    CAS  PubMed  Google Scholar 

  43. 43.

    Hernando-Herraez, I. et al. Nat. Commun. 10, 4361 (2019).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Saka, S. K. et al. Nat. Biotechnol. 37, 1080–1090 (2019).

    CAS  PubMed  Google Scholar 

  45. 45.

    Goltsev, Y. et al. Cell 174, 968–981.e15 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Gut, G., Herrmann, M. D. & Pelkmans, L. Science 361, eaar7042 (2018).

    PubMed  Google Scholar 

  47. 47.

    Marioni, J. C. & Arendt, D. Annu. Rev. Cell Dev. Biol. 33, 537–553 (2017).

    CAS  PubMed  Google Scholar 

  48. 48.

    Shafer, M. E. R. Front. Cell Dev. Biol. 7, 175 (2019).

    PubMed  PubMed Central  Google Scholar 

  49. 49.

    Camp, J. G., Platt, R. & Treutlein, B. Science 365, 1401–1405 (2019).

    CAS  PubMed  Google Scholar 

  50. 50.

    Wee, C. L. et al. Nat. Neurosci. 22, 1477–1492 (2019).

    CAS  PubMed  Google Scholar 

  51. 51.

    Lovett-Barron, M. et al. Preprint at bioRxiv https://doi.org/10.1101/745075 (2019).

  52. 52.

    Shah, S. et al. Cell 174, 363–376.e16 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Moor, A. E. et al. Science 357, 1299–1303 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Wan, Y. et al. Cell 179, 355–372.e23 (2019).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am grateful to J. Farrell, S. Mango and B. Raj for comments on the manuscript and to the US National Institutes of Health, the McKnight Endowment Fund for Neuroscience, the Allen Discovery Center for Cell Lineage Tracing, Harvard University and the University of Basel for support.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Alexander F. Schier.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schier, A.F. Single-cell biology: beyond the sum of its parts. Nat Methods 17, 17–20 (2020). https://doi.org/10.1038/s41592-019-0693-3

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing