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

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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

2 Citations (Scopus)


Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-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 Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-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 Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.

Original languageEnglish
Pages (from-to)4631
JournalNature Communications
Issue number1
Publication statusPublished - 02 Aug 2023


  • Humans
  • Plasmodium falciparum/genetics
  • Liver/metabolism
  • Hepatocytes/metabolism
  • Malaria/parasitology
  • Organoids/metabolism
  • Malaria, Falciparum/parasitology


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