More with Less: Single-cell Metabolomics by Mass Spectrometry
With the advent of techniques such as fluorescence activated cell sorting (FACS) and single-cell transcriptomics, research on the single-cell scale has become increasingly prevalent. Analysis of cells on a single-cell scale allows for accurate representation of the phenotype of rare cells, or cells in a heterogeneous population, which are often reduced to background signal when measured with traditional bulk analysis approaches. One approach particularly suited to describe the phenotype of single cells is single-cell metabolomics. Metabolites, compared to RNA and proteins, have fast turnover times, and metabolite levels can change quickly in response to cellular processes or stimuli. As such, the metabolome can serve as a powerful tool describing the cell's immediate state and phenotype. An inherent challenge of the metabolome's plasticity, however, is the risk of perturbing the metabolome by sampling and measuring a cell. As such, correct sampling and analysis strategies are essential to the outcome of a single-cell metabolomics experiment. In this chapter, we discuss the advantages and challenges of single-cell metabolomics and highlight several successful approaches and their uses.