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Mass spectrometry imaging: the rise of spatially resolved single-cell omics

Increasing evidence suggests that the spatial distribution of biomolecules within cells is a critical component in deciphering single-cell molecular heterogeneity. State-of-the-art single-cell MS imaging is uniquely capable of localizing biomolecules within cells, providing a dimension of information beyond what is currently available through in-depth omics investigations.

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Fig. 1: MS imaging of single cells at subcellular resolution.
Fig. 2: Obtaining high-content single-cell molecular information using a wide range of MS imaging platforms.

References

  1. Thul, P. J. et al. Science 356, eaal3321 (2017).

    Article  PubMed  Google Scholar 

  2. Pareek, V., Tian, H., Winograd, N. & Benkovic, S. J. Science 368, 283–290 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Cong, Y. Z. et al. Chem. Sci. 12, 1001–1006 (2021).

    Article  CAS  Google Scholar 

  5. Zhu, H. et al. Nat. Methods 18, 788–798 (2021).

    Article  CAS  PubMed  Google Scholar 

  6. Capolupo, L. et al. Science 376, eabh1623 (2022).

    Article  CAS  PubMed  Google Scholar 

  7. Keren, L. et al. Sci. Adv. 5, eaax5851 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Angelo, M. et al. Nat. Med. 20, 436–442 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Giesen, C. et al. Nat. Methods 11, 417–422 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Jackson, H. W. et al. Nature 578, 615–620 (2020).

    Article  CAS  PubMed  Google Scholar 

  11. Kuett, L. et al. Nat. Cancer 3, 122–133 (2022).

    Article  CAS  PubMed  Google Scholar 

  12. Bandura, D. R. et al. Anal. Chem. 81, 6813–6822 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Rendeiro, A. F. et al. Nature 593, 564–569 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yagnik, G., Liu, Z., Rothschild, K. J. & Lim, M. J. J. Am. Soc. Mass Spectrom. 32, 977–988 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Passarelli, M. K. et al. Nat. Methods 14, 1175–1183 (2017).

    Article  CAS  PubMed  Google Scholar 

  16. Yuan, Z. et al. Nat. Methods 18, 1223–1232 (2021).

    Article  CAS  PubMed  Google Scholar 

  17. Kompauer, M., Heiles, S. & Spengler, B. Nat. Methods 14, 90–96 (2017).

    Article  CAS  PubMed  Google Scholar 

  18. Niehaus, M., Soltwisch, J., Belov, M. E. & Dreisewerd, K. Nat. Methods 16, 925–931 (2019).

    Article  CAS  PubMed  Google Scholar 

  19. Castro, D. C., Xie, Y. R., Rubakhin, S. S., Romanova, E. V. & Sweedler, J. V. Nat. Methods 18, 1233–1238 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rappez, L. et al. Nat. Methods 18, 799–805 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, H. A. O. et al. Anal. Chem. 85, 10107–10116 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Stolee, J. A. & Vertes, A. Anal. Chem. 85, 3592–3598 (2013).

    Article  CAS  PubMed  Google Scholar 

  23. Li, X. et al. J. Am. Chem. Soc. 143, 21648–21656 (2021).

    Article  CAS  PubMed  Google Scholar 

  24. Yin, R., Burnum-Johnson, K. E., Sun, X., Dey, S. K. & Laskin, J. Nat. Protoc. 14, 3445–3470 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sparvero, L. J. et al. Angew. Chem. Int. Ed. 60, 11784–11788 (2021).

    Article  CAS  Google Scholar 

  26. Kuznetsov, I. et al. Nat. Commun. 6, 6944 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Li, L., Garden, R. W. & Sweedler, J. V. Trends Biotechnol. 18, 151–160 (2000).

    Article  CAS  PubMed  Google Scholar 

  28. Li, L. et al. Anal. Chem. 72, 3867–3874 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Jurchen, J. C., Rubakhin, S. S. & Sweedler, J. V. J. Am. Soc. Mass Spectrom. 16, 1654–1659 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Zhang, H. et al. Chem. Sci. 12, 8115–8122 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, G. Y. et al. Nat. Commun. 10, 4697 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Spraggins, J. M. et al. Anal. Chem. 91, 14552–14560 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Neumann, E. K. et al. Anal. Chem. 92, 13084–13091 (2020).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Aspects of this work were supported in part by the NIH grants R01 DK071801, R01 AG078794, RF1AG052324, P01CA250972, and the United States Department of Agriculture (grant number 2018-67001-28266). Some of our mass spectrometers were acquired using the NIH shared instrument grants S10OD028473, S10RR029531 and S10OD025084. H.Z. thanks for funding support a Postdoctoral Career Development Award provided by the American Society for Mass Spectrometry (2022). L.L. acknowledges a Pancreas Cancer Pilot grant from the University of Wisconsin Carbone Cancer Center (233-AAI9632), a Diabetes Research Center pilot and feasibility grant by Washington University/University of Wisconsin-Madison (grant No. P30 DK020579), and a Vilas Distinguished Achievement Professorship and Charles Melbourne Johnson Distinguished Chair Professorship with funding provided by the Wisconsin Alumni Research Foundation and the University of Wisconsin-Madison School of Pharmacy.

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H.Z., D.G.D. and L.L. wrote the manuscript and L.L. provided funding support. All authors participated in the discussion and edited the manuscript.

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Correspondence to Lingjun Li.

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Zhang, H., Delafield, D.G. & Li, L. Mass spectrometry imaging: the rise of spatially resolved single-cell omics. Nat Methods 20, 327–330 (2023). https://doi.org/10.1038/s41592-023-01774-6

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