Single-cell multi-omics in the medicinal plant Catharanthusroseus

Advances in omics technologies now permit the generation of highly contiguous genome assemblies, detection of transcripts and metabolites at the level of single cells and high-resolution determination of gene regulatory features. Here, using a complementary, multi-omics approach, we interrogated the monoterpene indole alkaloid (MIA) biosynthetic pathway in Catharanthus roseus, a source of leading anticancer drugs. We identified clusters of genes involved in MIA biosynthesis on the eight C. roseus chromosomes and extensive gene duplication of MIA pathway genes. Clustering was not limited to the linear genome, and through chromatin interaction data, MIA pathway genes were present within the same topologically associated domain, permitting the identification of a secologanin transporter. Single-cell RNA-sequencing revealed sequential cell-type-specific partitioning of the leaf MIA biosynthetic pathway that, when coupled with a single-cell metabolomics approach, permitted the identification of a reductase that yields the bis-indole alkaloid anhydrovinblastine. We also revealed cell-type-specific expression in the root MIA pathway.

Automated summary

Through genomic and single-cell analysis, we investigated the biosynthetic pathway of monoterpene indole alkaloids in Catharanthus roseus. We identified gene clusters and gene duplications involved in the pathway, as well as a transporter. Single-cell transcriptomics and metabolomics revealed cell-type-specific expression patterns and the identification of a reductase product. The study also uncovered cell-type-specific expression in the root pathway.