Single-cell multi-omics reveals that cell types are differentially involved in production and accumulation of medically relevant plant compounds Plants are impressive in their diversity, but especially in the variety of metabolites they produce. Many plant natural products are highly complex molecules, such as the alkaloids vincristine and vinblastine, which are produced by the Madagascar periwinkle Catharanthus roseus. These two substances are already indispensable in cancer therapy. Researchers are very interested in finding out which individual biosynthetic steps are required to form the complex molecules. "Currently, these compounds are still obtained in very small quantities from the plant's leaf extract. We can learn from the plant how this compound is produced and use this knowledge to develop production systems that are more cost-effective, scalable and sustainable," said first author Chenxin Li of the University of Georgia's Center for Applied Genetic Technologies. The scientists know that gene activity is not the same in all cells of a plant and that the chemistry can differ drastically from cell to cell. Therefore, the goal of the current study was to use a new set of methods collectively termed single-cell omics to investigate specialized and rare cell types that play a central role in the biosynthesis of plant natural products, and whose signals are often obscured by more abundant cell types in plant organs. "With single-cell omics, we have a method that allows researchers to assign genetic and metabolic information to individual cells. The term omics refers to the fact that an entire collection of genes or metabolites is quantified and analyzed," says Lorenzo Caputi, head of the Alkaloid Biosynthesis Project Group in the Department of Natural Product Biosynthesis in Jena and one of the lead authors, explaining the methodological approach. As the analyses showed, the entire biosynthetic pathway for the alkaloid vinblastine is organized in three stages and three discrete cell types. "The first stage is expressed exclusively in specialized cells associated with vascular bundles in the leaf, called IPAP. The second stage of the biosynthetic pathway is expressed only in cells of the epidermis, the layer of cells that cover the leaves, and the last known steps of the biosynthetic pathway are expressed exclusively in idioblasts, a rare cell type of the leaf," Chenxin Li summarizes the results. A better understanding of the biosynthetic pathways of the anti-cancer drugs vincristine and vinblastine may also help to produce or harvest these compounds more effectively in the long term. The use of methods described is also promising for the study of many other interesting and medically important natural products from the plant kingdom. The approach described here will help to narrow down these rare and specialized cells and uncover the gene activities and chemistry that are exclusive to them.
