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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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Main Authors: Cairns, James L. (Author) , Huber, Johanna (Author) , Lewen, Andrea (Author) , Jung, Jessica (Author) , Maurer, Stefan J. (Author) , Bausbacher, Tobias (Author) , Schmidt, Stefan (Author) , Levkin, Pavel (Author) , Sévin, Daniel Charles (Author) , Göpfrich, Kerstin (Author) , Koch, Philipp (Author) , Kann, Oliver (Author) , Hopf, Carsten (Author)
Format: Article (Journal)
Language:English
Published: February 3, 2025
In: Advanced science
Year: 2025, Volume: 12, Issue: 5, Pages: 1-15
ISSN:2198-3844
DOI:10.1002/advs.202410506
Online Access: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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Author Notes: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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Summary: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.
Item Description:Gesehen am 24.03.2025
Physical Description:Online Resource
ISSN:2198-3844
DOI:10.1002/advs.202410506

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