Dynamic single-cell transcriptomics reveals lsamp-guided neural network formation in male S. japonicum driving female reproduction

Sexual maturation and egg production in schistosomes require sustained male-female pairing, yet the cellular dynamics underlying this process remain poorly understood. Here, we generated a high-resolution single-cell transcriptomic atlas of 104,671 cells from male and female Schistosoma japonicum across four developmental stages, identifying 76 distinct cell populations and mapping lineage trajectories in reproductive and neural systems. Notably, we discovered three male-specific neuron subtypes, including delta-3 neurons located in the gynecophoric canal, and identified lsamp as a critical gene co-expressed with nrps in delta-3 neurons. Loss of lsamp impaired axonal growth and disrupted the male ventral nerve network, reducing the targeted delivery of pheromone BATT precursors to delta-3 neurons, thereby hindering female reproductive maturation. This work maps schistosome male-female interactions at single-cell resolution, revealing a male ventral nerve network that facilitates intersex communication and promotes female reproductive development, offering the new strategies to disrupt parasite reproduction and combat schistosomiasis.