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Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; Department of Global Health, Institut Pasteur, 25-28 Rue du Docteur Roux, Paris, France.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 7177Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2024. Vol. 15, no 1, article id 7177
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-229317DOI: 10.1038/s41467-024-51201-3ISI: 001304522300020PubMedID: 39187486Scopus ID: 2-s2.0-85202035496OAI: oai:DiVA.org:umu-229317DiVA, id: diva2:1897489
Funder
Swedish Research Council, VR 2021-05057Swedish Society for Medical Research (SSMF)Swedish Research Council, VR 2021-06602Available from: 2024-09-13 Created: 2024-09-13 Last updated: 2025-04-24Bibliographically approved

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Henriksson, Johan

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Molecular Infection Medicine Sweden (MIMS)Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)
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