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000292603 1001_ $$00009-0004-9100-314X$$aBuglakova, Elena$$b0
000292603 245__ $$aSpatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.
000292603 260__ $$a[London]$$bSpringer Nature$$c2024
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000292603 520__ $$aWhile 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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000292603 7001_ $$00000-0002-0917-9540$$aEkelöf, Måns$$b1
000292603 7001_ $$00000-0002-2715-753X$$aSchwaiger-Haber, Michaela$$b2
000292603 7001_ $$0P:(DE-He78)e52c8f6ae826320eaf2fb173e162070d$$aSchlicker, Lisa$$b3$$udkfz
000292603 7001_ $$00000-0001-5221-608X$$aMolenaar, Martijn R$$b4
000292603 7001_ $$aShahraz, Mohammed$$b5
000292603 7001_ $$aStuart, Lachlan$$b6
000292603 7001_ $$00000-0002-1113-9556$$aEisenbarth, Andreas$$b7
000292603 7001_ $$00000-0002-2255-2960$$aHilsenstein, Volker$$b8
000292603 7001_ $$00000-0002-3748-6193$$aPatti, Gary J$$b9
000292603 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b10$$eLast author$$udkfz
000292603 7001_ $$0P:(DE-He78)7b7131e0870c28d432e48873d295460f$$aSnaebjörnsson, Marteinn Thor$$b11$$eLast author$$udkfz
000292603 7001_ $$00000-0001-9464-6125$$aAlexandrov, Theodore$$b12
000292603 773__ $$0PERI:(DE-600)2933873-6$$a10.1038/s42255-024-01118-4$$n9$$p1695-1711$$tNature metabolism$$v6$$x2522-5812$$y2024
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