Journal Article

DKFZ-2024-01829

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Spatial single-cell isotope tracing reveals heterogeneity of de novo fatty acid synthesis in cancer.

Buglakova, E. ; Ekelöf, M. ; Schwaiger-Haber, M. ; Schlicker, L.DKFZ* ; Molenaar, M. R. ; Shahraz, M. ; Stuart, L. ; Eisenbarth, A. ; Hilsenstein, V. ; Patti, G. J. ; Schulze, A. (Last author)DKFZ* ; Snaebjörnsson, M. T. (Last author)DKFZ* ; Alexandrov, T.

2024
Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s42255-024-01118-4

Abstract: 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.

Note: DKFZ-ZMBH Alliance / #LA:A410# / 2024 Sep;6(9):1695-1711

---

Contributing Institute(s):

1. Metabolismus und Microenvironment (A410)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---