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

Nature Methods volume 20, pages 327–330 (2023)Cite this article

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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.

Cells are considered the fundamental building blocks of all living organisms. Despite knowing that the diversity of sophisticated activity needed to sustain life is a result of intercellular communications and molecular interactions, full comprehension of these biological mechanisms is lacking. To unravel this mystery, a spotlight has been turned toward single-cell omics analyses capable of deciphering cellular diversity and heterogeneity, in the hopes that characterizing cellular components will provide greater insights into single-cell physiological activity. With recent validation of capable analytical methodologies driving single-cell genomics, transcriptomics, proteomics and metabolomics investigations, holistic biomolecular investigations are now firmly within reach.

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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.

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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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Authors and Affiliations

  1. School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA

    Hua Zhang & Lingjun Li

  2. Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA

    Daniel G. Delafield & Lingjun Li

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  1. Hua Zhang
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  2. Daniel G. Delafield
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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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