Mass-guided single-cell MALDI imaging of low-mass metabolites reveals cellular activation markers
Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront of biomedical research and chemical biology. However, cell-targeting and metabolome-preserving methods for analysis of low mass, hydrophilic metabolites (<200 Da) in large cel...
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| Hauptverfasser: | , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 3, 2025
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| In: |
Advanced science
Year: 2025, Jahrgang: 12, Heft: 5, Pages: 1-15 |
| ISSN: | 2198-3844 |
| DOI: | 10.1002/advs.202410506 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/advs.202410506 Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202410506 
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| Verfasserangaben: | James L. Cairns, Johanna Huber, Andrea Lewen, Jessica Jung, Stefan J. Maurer, Tobias Bausbacher, Stefan Schmidt, Pavel A. Levkin, Daniel Sevin, Kerstin Göpfrich, Philipp Koch, Oliver Kann, Carsten Hopf |
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| 245 | 1 | 0 | |a Mass-guided single-cell MALDI imaging of low-mass metabolites reveals cellular activation markers |c James L. Cairns, Johanna Huber, Andrea Lewen, Jessica Jung, Stefan J. Maurer, Tobias Bausbacher, Stefan Schmidt, Pavel A. Levkin, Daniel Sevin, Kerstin Göpfrich, Philipp Koch, Oliver Kann, Carsten Hopf |
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| 520 | |a Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront of biomedical research and chemical biology. However, cell-targeting and metabolome-preserving methods for analysis of low mass, hydrophilic metabolites (<200 Da) in large cell populations are lacking. Here, the PRISM-MS (PRescan Imaging for Small Molecule - Mass Spectrometry) mass-guided MSI workflow is presented, which enables space-efficient single cell lipid and metabolite analysis. In conjunction with giant unilamellar vesicles (GUVs) as MSI ground truth for cell-sized objects and Monte Carlo reference-based consensus clustering for data-dependent identification of cell subpopulations, PRISM-MS enables MSI and on-cell MS2-based identification of low-mass metabolites like amino acids or Krebs cycle intermediates involved in stimulus-dependent cell activation. The utility of PRISM-MS is demonstrated through the characterization of complex metabolome changes in lipopolysaccharide (LPS)-stimulated microglial cells and human-induced pluripotent stem cell-derived microglia. Translation of single cell results to endogenous microglia in organotypic hippocampal slice cultures indicates that LPS-activation involves changes of the itaconate-to-taurine ratio and alterations in neuron-to-glia glutamine-glutamate shuttling. The data suggests that PRISM-MS can serve as a standard method in single cell metabolomics, given its capability to characterize larger cell populations and low-mass metabolites. | ||
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