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Development of Plasmodium falciparum liver stages in human fetal hepatocyte organoid cultures

ABSTRACT: Development of Plasmodium falciparum liver stages in human fetal hepatocyte organoid cultures

PROVIDER: PRJNA819014 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18453061_1.fastq.gz	Fastqsanger.gz
	SRR18453061_2.fastq.gz	Fastqsanger.gz
	SRR18453062_1.fastq.gz	Fastqsanger.gz
	SRR18453062_2.fastq.gz	Fastqsanger.gz
	SRR18453063_1.fastq.gz	Fastqsanger.gz

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Development of Plasmodium falciparum liver stages in human fetal hepatocyte organoid cultures

Project description: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 more than 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.

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

Project description: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.

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