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| Status |
Public on Aug 02, 2023 |
| Title |
Development of Plasmodium falciparum liver stages in human fetal hepatocyte organoid cultures |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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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| Overall design |
We generated single-cell transcriptome data from single cells purified from human hepatocyte organoids and human red blood cells that were exposed to Malaria parasite Plasmodium falciparum
|
| Web link |
https://www.nature.com/articles/s41467-023-40298-7
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| Contributor(s) |
Yang AS, Dutta D, Kretzschmar K, Hendriks D, Puschhof J, Hu H, Boonekamp KE, van Waardenburg Y, Chuva de Sousa Lopes SM, van Gemert G, de Wilt JH, Bousema T, Sauerwein RW, Clevers H |
| Citation(s) |
37532704 |
| |
| Submission date |
Mar 23, 2022 |
| Last update date |
Aug 03, 2023 |
| Contact name |
Kai Kretzschmar |
| E-mail(s) |
kai.kretzschmar@uni-wuerzburg.de
|
| Organization name |
University Hospital Würzburg
|
| Street address |
Josef-Schneider-Str. 2
|
| City |
Würzburg |
| ZIP/Postal code |
97080 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (6)
|
| GSM5967854 |
Single cells of human hepatoctye organoid cultures 4 days after the start of the experiment, control plate |
| GSM5967855 |
Single cells of human hepatoctye organoid cultures 4 days after infection, sample plate 1 |
| GSM5967856 |
Single cells of human hepatoctye organoid cultures 4 days after infection, sample plate 2 |
| GSM5967857 |
Single cells of human hepatoctye organoid cultures 5 days after the start of the experiment, control plate |
| GSM5967858 |
Single cells of human hepatoctye organoid cultures 5 days after infection, sample plate |
| GSM5967859 |
Extracted RNA from human erythrocytes infected with Plasmdoium falciparum |
|
| Relations |
| BioProject |
PRJNA819014 |
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