Single-cell analyses identify the ginseng embryonic protoderm as a native compartment for high-efficiency ginsenoside production

Ginseng (Panax ginseng) derives its renowned therapeutic properties from ginsenoside metabolites. However, the long cultivation cycle and susceptibility to diseases hinder the advancement of the ginseng industry. Here, we demonstrate that the embryonic protoderm of ginseng can efficiently produce ginsenosides. Single-cell transcriptome and mass spectrometry imaging analyses reveal that ginsenosides accumulate in the protoderm of ginseng embryonic callus (EC) at levels comparable to those in forest ginseng. Epigenetic analyses indicate that elevated histone acetylation and enhanced chromatin accessibility at regeneration- and ginsenoside metabolism-related gene loci are associated with the ginsenoside-producing capacity of EC. Increasing histone acetylation levels or overexpressing the regeneration-related WUSCHEL-RELATED HOMEOBOX11 (WOX11) gene further enhances ginsenoside production in EC. Our findings suggest that the protoderm of EC could serve as an in situ biological compartment for high-efficiency ginsenoside producion, offering a complementary approach to traditional ginseng cultivation. Liu et al. identify the ginseng embryonic protoderm as a native, ginsenoside-producing compartment through single-cell analysis. They further develop complementary epigenetic and genetic strategies to enhance metabolite output, presenting a scalable and sustainable alternative to conventional field cultivation.