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Making single-cell proteomics biologically relevant

Recent technological advances in mass spectrometry promise to add single-cell proteomics to the biologist’s toolbox. Here we discuss the current status and what is needed for this exciting technology to lead to biological insight — alone or as a complement to other omics technologies.

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Fig. 1: The dawn of single-cell proteomics.
Fig. 2: Approaching biology with sc-proteomics.

References

  1. Elmentaite, R., Domínguez Conde, C., Yang, L. & Teichmann, S. A. Nat. Rev. Genet. 23, 395–410 (2022).

    Article  CAS  PubMed  Google Scholar 

  2. Deng, Y. et al. Nature 609, 375–383, https://doi.org/10.1038/s41586-022-05094-1 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Milo, R., Jorgensen, P., Moran, U., Weber, G. & Springer, M. Nucleic Acids Res. 38, D750–D753 (2010).

    Article  CAS  PubMed  Google Scholar 

  4. Zhu, Y. et al. Nat. Commun. 9, 882 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Brunner, A.-D. et al. Mol. Syst. Biol. 18, e10798 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kelly, R. T. Mol. Cell. Proteomics 19, 1739–1748 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Stejskal, K., Op de Beeck, J., Dürnberger, G., Jacobs, P. & Mechtler, K. Anal. Chem. 93, 8704–8710 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Müller, J. B. et al. Nature 582, 592–596 (2020).

    Article  PubMed  Google Scholar 

  9. Sandow, J. J., Infusini, G., Dagley, L. F., Larsen, R. & Webb, A. I. Preprint at bioRxiv https://doi.org/10.1101/657908 (2021).

  10. Ludwig, C. et al. Mol. Syst. Biol. 14, e8126 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Demichev, V., Messner, C. B., Vernardis, S. I., Lilley, K. S. & Ralser, M. Nat. Methods 17, 41–44 (2020).

    Article  CAS  PubMed  Google Scholar 

  12. Bekker-Jensen, D. B. et al. Cell Syst. 4, 587–599.e4 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meier, F., Geyer, P. E., Virreira Winter, S., Cox, J. & Mann, M. Nat. Methods 15, 440–448 (2018).

    Article  CAS  PubMed  Google Scholar 

  14. Budnik, B., Levy, E., Harmange, G. & Slavov, N. Genome Biol. 19, 161 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cheung, T. K. et al. Nat. Methods 18, 76–83 (2021).

    Article  CAS  PubMed  Google Scholar 

  16. Ye, Z., Batth, T. S., Rüther, P. & Olsen, J. V. Commun. Biol. 5, 150 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Minogue, C. E. et al. Anal. Chem. 87, 2570–2575 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Derks, J. et al. Nat. Biotechnol. 41, 50–59 (2023).

    Article  CAS  PubMed  Google Scholar 

  19. Griffiths, J. R. et al. J. Am. Soc. Mass Spectrom. 25, 767–777 (2014).

    Article  CAS  PubMed  Google Scholar 

  20. Thielert, M. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.12.02.518917 (2022).

  21. Messner, C. B. et al. Nat. Biotechnol. 39, 846–854 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mund, A. et al. Nat. Biotechnol. 40, 1231–1240 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rosenberger, F. A. et al. Preprint at bioRxiv https://doi.org/10.1101/2022.12.03.518957 (2022).

  24. Kühl, I. et al. eLife 6, e30952 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the members of our single-cell and DVP teams in Munich and Copenhagen for discussions. The authors are supported by grants from the Max Planck Society for the Advancement of Science, Germany, and the European Union’s Horizon 2020 research and innovation program ISLET (No. 874839). F.A.R. is an EMBO postdoctoral fellowship holder (ALTF 399-2021). We thank Juliet Percival (Percival Press, Durham, UK) for the scientific illustrations.

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M.M., M.T. and F.A.R. conceived the original idea. M.M., F.A.R. and M.T. wrote and edited the original draft. F.A.R., M.T. and M.M. conceptualized and guided the illustration process. All authors wrote, edited and gave final approval to the manuscript.

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Correspondence to Matthias Mann.

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Competing interests

M.M. is an indirect shareholder in Evosep Biosystems. The remaining authors declare no competing interests.

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Rosenberger, F.A., Thielert, M. & Mann, M. Making single-cell proteomics biologically relevant. Nat Methods 20, 320–323 (2023). https://doi.org/10.1038/s41592-023-01771-9

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