Published July 27, 2021 | Version version 2.0

dual scRNA-seq analysis of P. vivax infected hepatocytes

Description

Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years, and then reactivate to cause recurrent blood-stage infection. While an important target for malaria eradication, little is known about the molecular features of the replicative and non-replicative states of intracellular P. vivax parasites, or their human host-cell dependencies and the host responses to them. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites in primary human hepatocytes and conduct transcriptional profiling. By coupling enrichment strategies with bulk and single-cell analyses, we captured both parasite and host transcripts in individual hepatocytes throughout the infection course. We define host- and state-dependent transcriptional signatures and identify previously unappreciated populations of replicative and non-replicative parasites, sharing features with sexual transmissive forms. We find that infection suppresses transcription of key hepatocyte function genes, and that P. vivax elicits an innate immune response that can be manipulated to control infection. Our work provides an extendible framework and resource for understanding host-parasite interactions and reveals new insights into the biology of P. vivax dormancy and transmission.

Notes

This repository contains the processed data (final selection of cells) supporting the analyses published in the Cell Host and Microbes article. Two time-course experiments were performed, from which corresponding SeqWell libraries were generated. These libraries were subsequently enriched for P. vivax-derived transcripts. Only post-enrichment, infected libraries were sequenced from "Experiment 1" - these are denoted "SEQ50" and "SEQ100" with respect to the parasite load used for infection. Regarding the second experiment reported here, both pre-captured (mostly host) and post-capture, infected libraries were sequenced. Therefore "Experiment 2" accounts for all the "host" data and all the P.vivax data annotated "SEQ1" or "SEQ2" (two replicates per infection for each time-point). "p" denotes treatment with a PI4K inhibitor. The files are organized as follows: - Host_compartment_CHM_final_object.RDS : Seurat object (R statistical environment) with filtered, pre-capture Experiment 2 data - Host_compartment_Final_CHM_counts.tar : MatrixMarket formatted count data, with cell names and gene names included as tab-separated files - PvData_CHM_Final.RDS : Seurat object (R statistical environment) with filtered, parasite-enriched data from Experiments 1 and 2 (cell names as referenced above) - PvData_CHM_Final_counts.csv.gz : comma-separated files of SCT-transformed parasite count data matching the PvData_CHM_Final.RDS object - TableS2_Cell_Metadata.xls : Metadata for all cells reported in this repository

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