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024 7 _ |a 10.1038/s42255-024-01118-4
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100 1 _ |a Buglakova, Elena
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245 _ _ |a Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.
260 _ _ |a [London]
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520 _ _ |a 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.
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700 1 _ |a Ekelöf, Måns
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700 1 _ |a Schwaiger-Haber, Michaela
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700 1 _ |a Schlicker, Lisa
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700 1 _ |a Molenaar, Martijn R
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700 1 _ |a Shahraz, Mohammed
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700 1 _ |a Stuart, Lachlan
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700 1 _ |a Eisenbarth, Andreas
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700 1 _ |a Hilsenstein, Volker
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700 1 _ |a Patti, Gary J
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700 1 _ |a Schulze, Almut
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700 1 _ |a Snaebjörnsson, Marteinn Thor
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700 1 _ |a Alexandrov, Theodore
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773 _ _ |a 10.1038/s42255-024-01118-4
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|t Nature metabolism
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856 4 _ |u https://inrepo02.dkfz.de/record/292603/files/s42255-024-01118-4.pdf
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