Single-cell RNA sequencing ofPlasmodiumvivax sporozoites reveals stage- and species-specific transcriptomic signatures

AbstractPlasmodium vivaxsporozoites reside in the salivary glands of a mosquito before infecting a human host. Previous transcriptome-wide studies in populations of these forms were limited in their ability to elucidate cell-to-cell variation, thereby masking cellular states potentially important in understanding transmission outcomes. In this study, we performed transcription profiling on 9,947P. vivaxsporozoites to assess the extent to which they differ at single-cell resolution. We show that sporozoites residing in the mosquito’s salivary glands exist in distinct developmental states, as defined by their transcriptomic signatures. Additionally, relative toP. falciparum, P. vivaxdisplays overlapping and unique gene usage patterns, highlighting conserved and species-specific gene programs. Notably, distinguishingP. vivaxfromP. falciparumwere a subset ofP. vivaxsporozoites expressing genes associated with translational regulation and repression. Finally, our comparison of single-cell transcriptomic data fromP. vivaxsporozoite and erythrocytic forms reveals gene usage patterns unique to sporozoites. In defining the transcriptomic signatures of individualP. vivaxsporozoites, our work provides new insights into the factors driving their developmental trajectory and lays the groundwork for a more comprehensiveP. vivaxcell atlas.