Single-cell metabolome and RNA-seq multiplexing on single plant cells

Plants produce valuable natural products used for a wide variety of industrial applications. Since these molecules have important applications in a variety of industrial sectors, there is enormous interest in elucidating the biosynthetic pathways that are responsible for the production of these compounds. Identification of the genes that comprise these biosynthetic pathways has been enabled by gene-to-metabolite networks that are generated from transcriptomic and metabolomic datasets. Recent advances in both single-cell RNA-seq (scRNA-seq) and single-cell mass spectrometry metabolomics (scMS) have enabled the measurement of either gene expression or metabolite levels in individual cells. However, these individual datasets can only be used to indirectly correlate gene expression levels with metabolite concentrations at the single cell level. Here we demonstrate that both scRNA-seq and scMS can be applied to the same plant cell, thereby enabling direct comparisons between gene expression and metabolite levels. This multiplexing approach reveals both qualitative and quantitative correlations between metabolite levels and biosynthetic gene expression in individual cells. This integrated approach sheds light on the underlying processes driving complex plant biosynthesis.