%0 Journal Article
%A Buglakova, Elena
%A Ekelöf, Måns
%A Schwaiger-Haber, Michaela
%A Schlicker, Lisa
%A Molenaar, Martijn R
%A Shahraz, Mohammed
%A Stuart, Lachlan
%A Eisenbarth, Andreas
%A Hilsenstein, Volker
%A Patti, Gary J
%A Schulze, Almut
%A Snaebjörnsson, Marteinn Thor
%A Alexandrov, Theodore
%T Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.
%J Nature metabolism
%V 6
%N 9
%@ 2522-5812
%C [London]
%I Springer Nature
%M DKFZ-2024-01829
%P 1695-1711
%D 2024
%Z DKFZ-ZMBH Alliance / #LA:A410# / 2024 Sep;6(9):1695-1711
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39251875
%R 10.1038/s42255-024-01118-4
%U https://inrepo02.dkfz.de/record/292603