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Spatial single-cell profiling of intracellular metabolomes in situ

View ORCID ProfileLuca Rappez, Mira Stadler, View ORCID ProfileSergio Triana, View ORCID ProfilePrasad Phapale, Mathias Heikenwalder, View ORCID ProfileTheodore Alexandrov
doi: https://doi.org/10.1101/510222
Luca Rappez
1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, 69117 Germany
2Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Germany
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Mira Stadler
3Institute of Chronic Inflammation and Cancer, Deutsches Krebs-Forschungszentrum (DKFZ), 69120 Heidelberg, Germany
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Sergio Triana
1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, 69117 Germany
2Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Germany
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Prasad Phapale
4Metabolomics Core Facility, EMBL, Heidelberg, 69117 Germany
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Mathias Heikenwalder
3Institute of Chronic Inflammation and Cancer, Deutsches Krebs-Forschungszentrum (DKFZ), 69120 Heidelberg, Germany
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Theodore Alexandrov
1Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, 69117 Germany
4Metabolomics Core Facility, EMBL, Heidelberg, 69117 Germany
5Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, CA 92093, La Jolla, USA
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  • For correspondence: theodore.alexandrov@embl.de
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Summary

The recently unveiled extent of cellular heterogeneity demands for single-cell investigations of intracellular metabolomes to reveal their roles in intracellular processes, molecular microenvironment and cell-cell interactions. To address this, we developed SpaceM, a method for in situ spatial single-cell metabolomics of cell monolayers which detects >100 metabolites in >10000 individual cells together with fluorescence and morpho-spatial cellular features. We discovered that the intracellular metabolomes of co-cultured human HeLa cells and mouse NIH3T3 fibroblasts predict the cell type with 90.4% accuracy and revealed a short-distance metabolic intermixing between HeLa and NIH3T3. We characterized lipid classes composing lipid droplets in steatotic differentiated human hepatocytes, and discovered a preferential accumulation of long-chain phospholipids, a co-regulation of oleic and linoleic acids, and an association of phosphatidylinositol monophosphate with high cell-cell contact. SpaceM provides single-cell metabolic, phenotypic, and spatial information and enables spatio-molecular investigations of intracellular metabolomes in a variety of cellular models.

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Posted January 02, 2019.
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Spatial single-cell profiling of intracellular metabolomes in situ
Luca Rappez, Mira Stadler, Sergio Triana, Prasad Phapale, Mathias Heikenwalder, Theodore Alexandrov
bioRxiv 510222; doi: https://doi.org/10.1101/510222
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Spatial single-cell profiling of intracellular metabolomes in situ
Luca Rappez, Mira Stadler, Sergio Triana, Prasad Phapale, Mathias Heikenwalder, Theodore Alexandrov
bioRxiv 510222; doi: https://doi.org/10.1101/510222

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