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Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer

While heterogeneity is a key feature of cancer, understanding metabolic heterogeneity at the single-cell level remains a challenge. Here we present 13C-SpaceM, a method for spatial single-cell isotope tracing that extends the previously published SpaceM method with detection of 13C6-glucose-derived...

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Main Authors: Buglakova, Elena (Author) , Ekelöf, Måns (Author) , Schwaiger-Haber, Michaela (Author) , Schlicker, Lisa (Author) , Molenaar, Martijn R. (Author) , Shahraz, Mohammed (Author) , Stuart, Lachlan (Author) , Eisenbarth, Andreas (Author) , Hilsenstein, Volker (Author) , Patti, Gary J. (Author) , Schulze, Almut (Author) , Snæbjörnsson, Marteinn (Author) , Alexandrov, Theodore (Author)
Format: Article (Journal)
Language:English
Published: 09 September 2024
In: Nature metabolism
Year: 2024, Volume: 6, Issue: 9, Pages: 1695-1711
ISSN:2522-5812
DOI:10.1038/s42255-024-01118-4
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s42255-024-01118-4
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s42255-024-01118-4
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Author Notes:Elena Buglakova, Måns Ekelöf, Michaela Schwaiger-Haber, Lisa Schlicker, Martijn R. Molenaar, Mohammed Shahraz, Lachlan Stuart, Andreas Eisenbarth, Volker Hilsenstein, Gary J. Patti, Almut Schulze, Marteinn T. Snaebjornsson & Theodore Alexandrov
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Summary:While heterogeneity is a key feature of cancer, understanding metabolic heterogeneity at the single-cell level remains a challenge. Here we present 13C-SpaceM, a method for spatial single-cell isotope tracing that extends the previously published SpaceM method with detection of 13C6-glucose-derived carbons in esterified fatty acids. We validated 13C-SpaceM on spatially heterogeneous models using liver cancer cells subjected to either normoxia-hypoxia or ATP citrate lyase depletion. This revealed substantial single-cell heterogeneity in labelling of the lipogenic acetyl-CoA pool and in relative fatty acid uptake versus synthesis hidden in bulk analyses. Analysing tumour-bearing brain tissue from mice fed a 13C6-glucose-containing diet, we found higher glucose-dependent synthesis of saturated fatty acids and increased elongation of essential fatty acids in tumours compared with healthy brains. Furthermore, our analysis uncovered spatial heterogeneity in lipogenic acetyl-CoA pool labelling in tumours. Our method enhances spatial probing of metabolic activities in single cells and tissues, providing insights into fatty acid metabolism in homoeostasis and disease.
Item Description:Gesehen am 07.03.2025
Physical Description:Online Resource
ISSN:2522-5812
DOI:10.1038/s42255-024-01118-4

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