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Yang, Annie S. P.; Dutta, Devanjali; Kretzschmar, Kai; Hendriks, Delilah; Puschhof, Jens; Hu, Huili; Boonekamp, Kim E.; van Waardenburg, Youri; Chuva de Sousa Lopes, Susana M.; van Gemert, Geert-Jan; de Wilt, Johannes H. W.; Bousema, Teun; Clevers, Hans; Sauerwein, Robert W.

Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures

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  • Medientyp: E-Artikel
  • Titel: Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures
  • Beteiligte: Yang, Annie S. P.; Dutta, Devanjali; Kretzschmar, Kai; Hendriks, Delilah; Puschhof, Jens; Hu, Huili; Boonekamp, Kim E.; van Waardenburg, Youri; Chuva de Sousa Lopes, Susana M.; van Gemert, Geert-Jan; de Wilt, Johannes H. W.; Bousema, Teun; Clevers, Hans; Sauerwein, Robert W.
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-40298-7
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p><jats:italic>Plasmodium falciparum</jats:italic> (<jats:italic>Pf</jats:italic>) parasite development in liver represents the initial step of the life-cycle in the human host after a <jats:italic>Pf-</jats:italic>infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for <jats:italic>Pf</jats:italic>-development and show that these cells permitted parasite invasion, differentiation and maturation of different <jats:italic>Pf</jats:italic> strains. Single-cell messenger RNA sequencing (scRNAseq) of <jats:italic>Pf-</jats:italic>infected HepOrg cells has identified 80 <jats:italic>Pf-</jats:italic>transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for <jats:italic>Pf</jats:italic> liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.</jats:p>
  • Zugangsstatus: Freier Zugang