Genetically identical cells are known to exhibit differential phenotypes in the same environmental conditions. These phenotypic variants are linked to transcriptional stochasticity and have been shown to contribute towards adaptive flexibility of a wide range of unicellular organisms. Here, we investigated transcriptional heterogeneity and stochastic gene expression in P. falciparum by performing single cell RNA sequencing on blood stage schizonts. Our data reveals significant transcriptional variations in the schizonts stage with a distinct group of highly variable invasion gene transcripts being identified. Moreover, our data reflected several diversification processes including putative developmental 鈥渃heckpoint鈥? transcriptomically distinct parasite sub-populations and transcriptional switches in variable gene families (var, rifin, phist). Most of these features of transcriptional variability were preserved in isogenic parasite cell populations (albeit with a lesser amplitude) suggesting a role of epigenetic factors in cell-to-cell transcriptional variations in human malaria parasites. Lastly, we applied quantitative RT-PCR and RNA-FISH approach and confirmed stochastic expression of merozoites surface proteins encoding msp1, msp3, msp7, rhoptry protein encoding rhopH2 and erythrocyte binding antigen encoding eba181, some of which represent key candidates for invasion blocking vaccines.

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Schizonts Stochastic Invasion P.

Zhu, Lei, Nayak, Sourav, Bozdech, Zbynek, Stoklasa, Michal,Tripathi, Jaishree,.Stochastic Expression of Invasion Genes in Plasmodium falciparum Schizonts. (),.

Zhu, Lei, et al."Stochastic Expression of Invasion Genes in Plasmodium falciparum Schizonts"

Zhu, Lei, Nayak, Sourav, Bozdech, Zbynek, Stoklasa, Michal,Tripathi, Jaishree,"Stochastic Expression of Invasion Genes in Plasmodium falciparum Schizonts"