Single-cell RNA sequencing provides a high-resolution roadmap for understanding the multicellular compartmentation of specialized metabolism

• Published in: Nature plants Vol. 9; no. 1; pp. 179 - 190
• Main Authors: Sun, Sijie, Shen, Xiaofeng, Li, Yi, Li, Ying, Wang, Shu, Li, Rucan, Zhang, Huibo, Shen, Guoan, Guo, Baolin, Wei, Jianhe, Xu, Jiang, St-Pierre, Benoit, Chen, Shilin, Sun, Chao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2023; Nature Publishing Group
• Subjects: 38/39; 38/77; 38/90; 38/91; 45/22; 45/23; 631/449/2653/2658; 631/449/2667; Alkaloids; Biological activity; Biomedical and Life Sciences; Biosynthesis; Compartmentation; Gene Expression Regulation, Plant; Gene sequencing; Genetic resources; Host plants; Hybridization; Indigenous plants; Intermediates; Leaves; Life Sciences; Metabolic engineering; Metabolism; Metabolites; Model updating; Plant Sciences; Resource; Ribonucleic acid; RNA; Secologanin Tryptamine Alkaloids - metabolism; Sequence Analysis, RNA; Spatial distribution; Temporal distribution; Transcriptomics
• DOI: 10.1038/s41477-022-01291-y
• ISSN: 2055-0278; 2055-026X

Monoterpenoid indole alkaloids (MIAs) are among the most diverse specialized metabolites in plants and are of great pharmaceutical importance. We leveraged single-cell transcriptomics to explore the spatial organization of MIA metabolism in Catharanthus roseus leaves, and the transcripts of 20 MIA genes were first localized, updating the model of MIA biosynthesis. The MIA pathway was partitioned into three cell types, consistent with the results from RNA in situ hybridization experiments. Several candidate transporters were predicted to be essential players shuttling MIA intermediates between inter- and intracellular compartments, supplying potential targets to increase the overall yields of desirable MIAs in native plants or heterologous hosts through metabolic engineering and synthetic biology. This work provides not only a universal roadmap for elucidating the spatiotemporal distribution of biological processes at single-cell resolution, but also abundant cellular and genetic resources for further investigation of the higher-order organization of MIA biosynthesis, transport and storage. The compartmentation of monoterpenoid indole alkaloid biosynthesis in periwinkle leaves was determined using single-cell RNA-seq, which reveals the spatial distribution of plant specialized metabolism at the single-cell resolution.