Comparative Single-Cell Transcriptomics Reveals Divergent Stage Transition Dynamics and Regulatory Strategies in Lab-Adapted and Field Isolates of Plasmodium falciparum

Abstract: The malaria parasite Plasmodium falciparum undergoes tightly regulated stage transitions during its intraerythrocytic development, but the dynamics of these transitions may differ between parasites adapted to laboratory conditions and those circulating in natural human hosts. To investigate these differences, we performed a comparative single-cell transcriptomic analysis leveraging a dataset of 45,691 parasite cells, combining laboratory strains with field isolates from asymptomatic patients. We mapped developmental trajectories using PAGA-based trajectory inference, identified dynamic gene expression modules through differential gene expression analysis, and pinpointed candidate master regulators. Our analysis revealed that laboratory strains exhibit a continuous asexual developmental cycle, while field isolates are skewed towards sexual stages. Notably, we observed that candidate master regulators in laboratory strains show a 'just-in-time' activation pattern, with expression preceding downstream gene expression by a short interval. In contrast, field isolates displayed a 'priming' regulatory strategy, where regulators are expressed long before their target genes are activated. These findings suggest that P. falciparum adapts its stage progression control in response to the host environment, potentially reflecting an adaptation to ensure efficient transmission in the complex and variable environment of the human host. \

Subjects:	q-bio.GN; q-bio.QM
Cite as:	PX:2508.00003