In Situ Isotope Tracing at Single-Cell Resolution Using Mass Spectrometry Imaging

Mass spectrometry imaging (MSI) allows for label-free spatial molecular interrogation of tissues. With advances in the field over recent years, the spatial resolution at which MSI data can be recorded has reached the single-cell level. This makes MSI complementary to other single-cell omics technologies. As metabolism is a highly dynamic process, capturing the metabolic turnover adds a valuable layer of information. Here, we describe how to set up in situ stable isotope tracing followed by MSI-enabled spatial metabolomics to perform dynamic metabolomics at the single-cell level.