TY - JOUR AU - Rappez, Luca AU - Stadler, Mira AU - Triana, Sergio AU - Gathungu, Rose Muthoni AU - Ovchinnikova, Katja AU - Phapale, Prasad AU - Heikenwalder, Mathias AU - Alexandrov, Theodore TI - SpaceM reveals metabolic states of single cells. JO - Nature methods VL - 18 IS - 7 SN - 1548-7105 CY - London [u.a.] PB - Nature Publishing Group M1 - DKFZ-2021-01537 SP - 799-805 PY - 2021 N1 - #EA:F180# / 2021 Jul;18(7):799-805 / #DKFZ-MOST-Ca197# AB - A growing appreciation of the importance of cellular metabolism and revelations concerning the extent of cell-cell heterogeneity demand metabolic characterization of individual cells. We present SpaceM, an open-source method for in situ single-cell metabolomics that detects >100 metabolites from >1,000 individual cells per hour, together with a fluorescence-based readout and retention of morpho-spatial features. We validated SpaceM by predicting the cell types of cocultured human epithelial cells and mouse fibroblasts. We used SpaceM to show that stimulating human hepatocytes with fatty acids leads to the emergence of two coexisting subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine interleukin-17A perturbs the balance of these states in a process dependent on NF-κB signaling. The metabolic state markers were reproduced in a murine model of nonalcoholic steatohepatitis. We anticipate SpaceM to be broadly applicable for investigations of diverse cellular models and to democratize single-cell metabolomics. LB - PUB:(DE-HGF)16 C6 - pmid:34226721 DO - DOI:10.1038/s41592-021-01198-0 UR - https://inrepo02.dkfz.de/record/169732 ER -