Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis

Mubasher Mohammed (), Alexis Dziedziech, Diego Macedo, Frederik Huppertz, Ylva Veith, Zoé Postel, Elena Christ, Richard Scheytt, Tanja Slotte, Johan Henriksson and Johan Ankarklev ()
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Mubasher Mohammed: Stockholm University
Alexis Dziedziech: Stockholm University
Diego Macedo: Stockholm University
Frederik Huppertz: Stockholm University
Ylva Veith: Stockholm University
Zoé Postel: Stockholm University
Elena Christ: Stockholm University
Richard Scheytt: Stockholm University
Tanja Slotte: Stockholm University
Johan Henriksson: Umeå University
Johan Ankarklev: Stockholm University

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract The Plasmodium falciparum life cycle includes obligate transition between a human and mosquito host. Gametocytes are responsible for transmission from the human to the mosquito vector where gamete fusion followed by meiosis occurs. To elucidate how male and female gametocytes differentiate in the absence of sex chromosomes, we perform FACS-based cell enrichment of a P. falciparum gametocyte reporter line followed by single-cell RNA-seq. In our analyses we define the transcriptional programs and predict candidate driver genes underlying male and female development, including genes from the ApiAP2 family of transcription factors. A motif-driven, gene regulatory network analysis indicates that AP2-G5 specifically modulates male development. Additionally, genes linked to the inner membrane complex, involved in morphological changes, are uniquely expressed in the female lineage. The transcriptional programs of male and female development detailed herein allow for further exploration of the evolution of sex in eukaryotes and provide targets for future development of transmission blocking therapies.

Date: 2024
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DOI: 10.1038/s41467-024-51201-3

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