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    Transcriptional heterogeneity and tightly regulated changes in gene expression during Plasmodium berghei sporozoite development

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    Author
    Bogale, Haikel N
    Pascini, Tales V
    Kanatani, Sachie
    Sá, Juliana M
    Wellems, Thomas E
    Sinnis, Photini
    Vega-Rodríguez, Joel
    Serre, David
    Date
    2021-03-09
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    Publisher
    National Academy of Sciences
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1073/pnas.2023438118
    Abstract
    Despite the critical role of Plasmodium sporozoites in malaria transmission, we still know little about the mechanisms underlying their development in mosquitoes. Here, we use single-cell RNA sequencing to characterize the gene expression profiles of 16,038 Plasmodium berghei sporozoites isolated throughout their development from midgut oocysts to salivary glands, and from forced salivation experiments. Our results reveal a succession of tightly regulated changes in gene expression occurring during the maturation of sporozoites and highlight candidate genes that could play important roles in oocyst egress, sporozoite motility, and the mechanisms underlying the invasion of mosquito salivary glands and mammalian hepatocytes. In addition, the single-cell data reveal extensive transcriptional heterogeneity among parasites isolated from the same anatomical site, suggesting that Plasmodium development in mosquitoes is asynchronous and regulated by intrinsic as well as environmental factors. Finally, our analyses show a decrease in transcriptional activity preceding the translational repression observed in mature sporozoites and associated with their quiescent state in salivary glands, followed by a rapid reactivation of the transcriptional machinery immediately upon salivation.
    Rights/Terms
    Copyright © 2021 the Author(s). Published by PNAS.
    Keyword
    gene expression
    malaria
    single-cell analysis
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15295
    ae974a485f413a2113503eed53cd6c53
    10.1073/pnas.2023438118
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