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 generate 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 discover a male-specific neuron subtype - N4.3 neuron located in the gynecophoric canal, and identify lsamp as a critical gene co-expressed with nrps in N4.3 neurons. Loss of lsamp impairs axonal integrity and disrupts the male ventral nerve network, reducing the targeted delivery of pheromone BATT precursor to N4.3 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 strategies to disrupt parasite reproduction and combat schistosomiasis.