Divergent Transcriptional Programs and Regulatory Networks Govern Plasmodium falciparum Development in Laboratory-Adapted Strains and Field Isolates

Abstract: Laboratory adaptation can significantly alter Plasmodium falciparum biology, impacting the relevance of research findings. To understand these effects, we investigated differences in the dynamic transcriptional programs and regulatory networks governing stage transitions between lab-adapted strains and field isolates. Using single-cell RNA sequencing data from 45,691 cells, including both lab strains and field isolates from asymptomatic patients, we reconstructed and compared developmental trajectories, performed differential gene expression analysis, and identified co-expression modules and candidate regulators. Our analysis revealed substantial differences in transcriptional profiles, developmental trajectories, and regulatory networks between lab and field parasites, particularly during sexual development. We observed distinct expression patterns, alternative developmental routes in field isolates leading to late-stage gametocytes absent in lab strains, and a rewiring of regulatory networks. Specifically, we identified a unique set of candidate master regulators and inferred regulatory interactions in field isolates, suggesting adaptation to in vivo conditions alters developmental control and fate determination. These findings highlight the importance of studying field isolates to fully understand P. falciparum biology and the molecular mechanisms underlying parasite adaptation to the human host. \

Subjects:	q-bio.GN; q-bio.QM
Cite as:	PX:2508.00018