1. Cell Biology
  2. Microbiology and Infectious Disease
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A single-parasite transcriptional atlas of Toxoplasma gondii reveals novel control of antigen expression

  1. Yuan Xue
  2. Terence C Theisen
  3. Suchita Rastogi
  4. Abel Ferrel
  5. Stephen R Quake  Is a corresponding author
  6. John C Boothroyd  Is a corresponding author
  1. Stanford University, United States
  2. Stanford University School of Medicine, United States
  3. Chan Zuckerberg Biohub, United States
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Cite this article as: eLife 2020;9:e54129 doi: 10.7554/eLife.54129

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.

Article and author information

Author details

  1. Yuan Xue

    Department of Bioengineering, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7846-4273
  2. Terence C Theisen

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Suchita Rastogi

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Abel Ferrel

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephen R Quake

    Chan Zuckerberg Biohub, San Francisco, United States
    For correspondence
    steve@quake-lab.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1613-0809
  6. John C Boothroyd

    Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
    For correspondence
    jboothr@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9719-745X

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

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: December 3, 2019
  2. Accepted: February 16, 2020
  3. Accepted Manuscript published: February 17, 2020 (version 1)

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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