Spatial Single-Cell Metabolomics Reveals Metabolic Cell States
Recent discoveries put metabolism into the spotlight. Metabolism not only fuels cells but also plays key roles in health and disease in particular in cancer, inflammation, and immunity. In parallel, emerging single-cell technologies opened a new world of cell types and states previously hidden beneath population averages. Yet, methods for discovering links between metabolism, cell states, metabolic plasticity and reprogramming on the single-cell level and in situ are crucially lacking. Our research aims to bridge this gap. First, I will explain how the emerging technology of imaging mass spectrometry can be used for the spatial profiling of metabolites, lipids, and drugs in tissues. I will present our cloud and Artificial Intelligence-powered platform METASPACE which is increasingly used across the world. In the second part of my talk I will present our method SpaceM for spatial single-cell metabolomics in situ. SpaceM detects >100 metabolites from >1,000 individual cells/hour together with a fluorescence based read-out and morpho-spatial features. We used SpaceM to show that stimulating human hepatocytes with fatty acids led to the emergence of two co-existing subpopulations outlined by distinct cellular metabolic states. Inducing inflammation with the cytokine IL-17A perturbs the balance of these states in a process dependent on NF-κB signalling. The metabolic-state markers were reproduced in a pre-clinical in vivo murine model of non-alcoholic steatohepatitis. Overall, such methods open novel avenues for understanding metabolism in tissues and cell cultures on the single-cell level.
Theodore Alexandrov is a team leader at the European Molecular Biology Laboratory (EMBL), the Europe’s leading life science laboratory. He is also the head of the EMBL Metabolomics Core Facility and a faculty of the Molecular Medicine Partnership Unit between EMBL and Heidelberg University. The Alexandrov team at EMBL aims to reveal the secrets of metabolism in time and space in tissues and single cells by developing experimental and computational methods. The team of 20 members unites interdisciplinary scientists from biology, chemistry, and computer science as well as software engineers and data analysts. Their computational methods were included into various open-source and industrial software packages. Since 2014, the team develops and provides for free the cloud software METASPACE for metabolite ID in imaging mass spectrometry, which is used by universities, governmental organizations, and pharma companies. Theodore Alexandrov is a grantee of an ERC Consolidator project focused on studying metabolism in single cells, as well as of various other European, national, NIH, and industrially-funded projects. He has co-founded and scientifically directed the company SCiLS and has over 95 journal publications and 6 patents in the field of spatial and single-cell -omics.
Contact and Affiliation
European Molecular Biology Laboratory, Heidelberg, Germany