Single-nucleus transcriptomics reveal the morphogenesis and artemisinin biosynthesis in Artemisia annua glandular trichomes

Minghui Zhang, Mingyu Li, Yanyan An, Chang Liu, Qiaojuan Zhao, Danfeng Zhang, Baiwei Pan and Hexin Tan ()
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Minghui Zhang: Naval Medical University
Mingyu Li: Naval Medical University
Yanyan An: Naval Medical University
Chang Liu: Naval Medical University
Qiaojuan Zhao: Naval Medical University
Danfeng Zhang: Naval Medical University
Baiwei Pan: Naval Medical University
Hexin Tan: Naval Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Artemisinin, the key antimalarial drug, is synthesized in Artemisia annua glandular secretory trichomes (GSTs), yet their development and artemisinin’s precise cellular origins are unclear. Utilizing single-nucleus RNA sequencing and spatial transcriptomics, we construct a high-resolution cellular atlas mapping metabolic dynamics across GST development. We define three developmental states: the initiation phase, transcriptional activation of core metabolic pathways establishes fundamental cellular machinery; the intermediate phase, marked lipid metabolism activation with coordinated fatty acid and wax biosynthesis, accompanied by active photosynthetic activity; the terminal differentiation phase, metabolite specialized through spatial compartmentalization of terpenoid and lipid biosynthetic pathways. Notably, we discover that six specific secretory cells within the 10-cell GSTs constitute the primary site for artemisinin production. We identify hundreds of hub genes potentially contributing to trichome development or artemisinin biosynthesis. Overall, this study systematically elucidates GST development and artemisinin biosynthesis, revealing its spatial production mechanism and providing essential cellular and genetic foundations for metabolic engineering and fundamental trichome biology.

Date: 2025
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DOI: 10.1038/s41467-025-63770-y

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