Spatial single-cell metabolomics: A technology integrating microscopy and imaging mass spectrometry

Theodore Alexandrov and Volker Hilsenstein (EMBL)
Abstract: Recent discoveries put metabolism into the spotlight. Metabolism not only fuels cells but also plays key roles in health and disease. 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, we will present how the emerging technology of imaging mass spectrometry can be used for the spatial profiling of metabolites, lipids, and drugs in tissues. Second, we will present our method SpaceM for spatial single-cell metabolomics. SpaceM can analyze cells cultured or plated on a glass slide and deliver a metabolic profile of 100+ metabolites or 500+ lipids from thousands of individual cells combined with spatial, morphological and fluorescence features from light microscopy. This is achieved by integrating microscopy and imaging mass spectrometry of cells in multiple steps of image analysis, registration, and data integration. We will discuss the challenges and solutions associated with image analysis and spatial data integration in SpaceM and our current work to adapt the method for high-throughput. We will present how we leverage modern tools and file formats such as napari, dask and ngff for data acquisition, analysis, visualization and integration.