A single-parasite transcriptional atlas of Toxoplasma gondii reveals novel control of antigen expression
Abstract
Toxoplasma gondii, a protozoan parasite, undergoes a complex and poorly understood developmental process that is critical for establishing a chronic infection in its intermediate hosts. Here, we applied single-cell RNA-sequencing (scRNA-seq) on >5,400 Toxoplasma in both tachyzoite and bradyzoite stages using three widely studied strains to construct a comprehensive atlas of cell-cycle and asexual development, revealing hidden states and transcriptional factors associated with each developmental stage. Analysis of SAG1-related sequence (SRS) antigenic repertoire reveals a highly heterogeneous, sporadic expression pattern unexplained by measurement noise, cell cycle, or asexual development. Furthermore, we identified AP2IX-1 as a transcription factor that controls the switching from the ubiquitous SAG1 to rare surface antigens not previously observed in tachyzoites. In addition, comparative analysis between Toxoplasma and Plasmodium scRNA-seq results reveals concerted expression of gene sets, despite fundamental differences in cell division. Lastly, we built an interactive data-browser for visualization of our atlas resource.
Data availability
Instructions to obtain processed data, preprocessing scripts, and analysis scripts are available on https://github.com/xuesoso/singleToxoplasmaSeq.Raw fastq files and processed data are deposited on SRA and GEO repository (GEO number: GSE145080)
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Data from: A single-parasite transcriptional landscape of Toxoplasma gondii reveals novel control of antigen expressionDryad Digital Repository, 10.5061/dryad.kprr4xh17.
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Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of toxoplasma gondiiNCBI Gene Expression Omnibus, GSE19092.
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Transcriptomics of Toxoplasma gondii enteroepithelial stagesNCBI Gene Expression Omnibus, GSE108740.
Article and author information
Author details
Funding
Stanford University (Stanford Interdisciplinary Graduate Bio-X Fellowships)
- Yuan Xue
- Terence C Theisen
National Institutes of Health (F30 AI124589-03)
- Suchita Rastogi
National Institutes of Health (5T32AI007328-30)
- Abel Ferrel
Howard Hughes Medical Institute (Gilliams Fellowship for Advanced Study)
- Abel Ferrel
National Institutes of Health (RO1 AI21423)
- John C Boothroyd
National Institutes of Health (RO1 AI29529)
- John C Boothroyd
Chan Zuckerberg Biohub
- Stephen R Quake
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Dominique Soldati-Favre, University of Geneva, Switzerland
Version history
- Received: December 3, 2019
- Accepted: February 16, 2020
- Accepted Manuscript published: February 17, 2020 (version 1)
- Version of Record published: April 23, 2020 (version 2)
Copyright
© 2020, Xue et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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