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

Haikel N. Bogale, Tales V. Pascini, Sachie Kanatani, Juliana M. Sá, Thomas E. Wellems, Photini Sinnis, Joel Vega-Rodríguez, David Serre

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere2023438118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - Mar 9 2021
Externally publishedYes


  • Gene expression
  • Malaria
  • Single-cell analysis

ASJC Scopus subject areas

  • General


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