Spatial biology using single-cell mass spectrometry imaging and integrated microscopy

Alexander Potthoff, Jan Schwenzfeier, Marcel Niehaus, Sebastian Bessler, Emily Hoffmann, Oliver Soehnlein, Jens Höhndorf, Klaus Dreisewerd and Jens Soltwisch ()
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Alexander Potthoff: University of Münster
Jan Schwenzfeier: University of Münster
Marcel Niehaus: Bruker Daltonics GmbH & Co. KG
Sebastian Bessler: University of Münster
Emily Hoffmann: University of Münster
Oliver Soehnlein: University of Münster
Jens Höhndorf: Bruker Daltonics GmbH & Co. KG
Klaus Dreisewerd: University of Münster
Jens Soltwisch: University of Münster

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Spatial biology pursues the analysis of cells in their native microenvironment, often with regard to morphology and gene- or protein expression. The spatial analysis of lipid and metabolic profiles by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can add another layer of molecular information. A seamless integration of MSI data with other (multimodal) methods at a single-cell level is often hampered by insufficient co-registration and resolution. Here, we introduce a MALDI-MSI based method that integrates in-source bright-field and fluorescence microscopy, allowing for a coupled (sub-)cellular investigation of the same sample in both modalities. Presented examples from cell culture and tissue analysis include the visualization of intracellular lipid distributions in macrophages during phagocytosis, and the heterogeneity of lipid profiles of tumor infiltrating neutrophils correlated to their individual microenvironments. The achieved combination of lipid profiling with morphological features and protein expression on the single-cell level constitutes a powerful method for cell biology.

Date: 2025
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DOI: 10.1038/s41467-025-64603-8

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