Probing Plasmodium falciparum sexual differentiation at the single cell level

Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel events that initiate sexual development in preparation for transmission of the parasite from human to mosquito. This proof-of-concept study provides a template to capture transcriptional diversity in heterogeneous parasite populations, with major implications for our understanding of parasite biology and the ongoing malaria elimination campaign. Plasmodium-infected human erythrocytes were single-cell sorted into 384-well plates at three separate time points after LysoPC depletion gametocyte induction (4, 8, 12 hours post induction). Two rows (total of 48 wells) of each 384-well plate were reserved for control samples (no induction). A total of 1152 wells were sequenced, with 144 control wells, and 1008 induced wells.