TY  - JOUR
AU  - Buglakova, Elena
AU  - Ekelöf, Måns
AU  - Schwaiger-Haber, Michaela
AU  - Schlicker, Lisa
AU  - Molenaar, Martijn R
AU  - Shahraz, Mohammed
AU  - Stuart, Lachlan
AU  - Eisenbarth, Andreas
AU  - Hilsenstein, Volker
AU  - Patti, Gary J
AU  - Schulze, Almut
AU  - Snaebjörnsson, Marteinn Thor
AU  - Alexandrov, Theodore
TI  - Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.
JO  - Nature metabolism
VL  - 6
IS  - 9
SN  - 2522-5812
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2024-01829
SP  - 1695-1711
PY  - 2024
N1  - DKFZ-ZMBH Alliance / #LA:A410# / 2024 Sep;6(9):1695-1711
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:39251875
DO  - DOI:10.1038/s42255-024-01118-4
UR  - https://inrepo02.dkfz.de/record/292603
ER  -