Single-cell Transcriptomics Reveals Patient-Specific Heterogeneity in Transiently Expressed Regulators of Plasmodium falciparum Gametocytogenesis in Field Isolates

Abstract: Malaria transmission hinges on the development of Plasmodium falciparum gametocytes within the human host, yet the regulatory mechanisms driving this process in vivo remain poorly understood. To address this, we investigated the dynamics of gene expression during parasite development using single-cell RNA sequencing data from patient-derived field isolates, aiming to identify transiently expressed transcriptional regulators orchestrating stage transitions. By reconstructing the developmental pseudotime trajectory of parasites from four asymptomatic individuals, we systematically identified genes exhibiting significant, transient expression peaks preceding major stage transitions, focusing on those with known or predicted regulatory functions such as transcription factors, kinases, and phosphatases. Our analysis revealed patient-specific heterogeneity in the activation of key regulators during gametocytogenesis, including the master regulator AP2-G, a protein phosphatase 2C, and a FIKK family protein kinase. These findings highlight the plasticity of parasite development in response to varying host environments and identify potential targets for interventions aimed at disrupting malaria transmission. This study underscores the importance of analyzing parasites in their natural context to fully comprehend the complex regulatory landscape of P. falciparum. \

Subjects:	q-bio.GN; q-bio.QM
Cite as:	PX:2508.00019