Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni

  1. George R Wendt
  2. Julie NR Collins
  3. Jimin Pei
  4. Mark S Pearson
  5. Hayley M Bennett
  6. Alex Loukas
  7. Matthew Berriman
  8. Nick V Grishin
  9. James J Collins  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. James Cook University, Australia
  3. Wellcome Trust Sanger Institute, United Kingdom

Abstract

Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer-coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification. These proteins are homologous to a protein essential for neoblast-driven epidermal maintenance in free-living flatworms. Therefore, we speculate that related parasites (i.e., tapeworms and flukes) employ similar strategies to control tegumental maintenance. Since parasitic flatworms infect every vertebrate species, understanding neoblast-driven tegumental maintenance could identify broad-spectrum therapeutics to fight diseases caused by these parasites.

Data availability

The following data sets were generated
    1. Wellcome Trust Sanger Institute
    (2017) Characterising_Schistosoma_mansoni_stem_cell_populations
    ERS1987962, ERS1987961, ERS1987958, ERS1987958, ERS1987957, ERS1987948, ERS1987946, ERS1987945, ERS1987942.

Article and author information

Author details

  1. George R Wendt

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Julie NR Collins

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jimin Pei

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mark S Pearson

    Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0002-1544
  5. Hayley M Bennett

    Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Alex Loukas

    Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew Berriman

    Wellcome Trust Sanger Institute, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9581-0377
  8. Nick V Grishin

    Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. James J Collins

    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    JamesJ.Collins@UTSouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5237-1004

Funding

National Institutes of Health (R01AI121037)

  • James J Collins

Wellcome (107475/Z/15/Z)

  • Matthew Berriman
  • James J Collins

National Institutes of Health (R01GM094575)

  • Nick V Grishin

Welch Foundation (I1505)

  • Nick V Grishin

National Health and Medical Research Council

  • Alex Loukas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Nipam H Patel, University of California, Berkeley, United States

Ethics

Animal experimentation: In adherence to the Animal Welfare Act and the Public Health Service Policy on Humane Care and Use of Laboratory Animals, all experiments with and care of vertebrate animals were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the UT Southwestern Medical Center (protocol approval number APN 2014-0072).

Version history

  1. Received: October 30, 2017
  2. Accepted: March 19, 2018
  3. Accepted Manuscript published: March 20, 2018 (version 1)
  4. Version of Record published: April 30, 2018 (version 2)
  5. Version of Record updated: August 20, 2018 (version 3)

Copyright

© 2018, Wendt 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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  1. George R Wendt
  2. Julie NR Collins
  3. Jimin Pei
  4. Mark S Pearson
  5. Hayley M Bennett
  6. Alex Loukas
  7. Matthew Berriman
  8. Nick V Grishin
  9. James J Collins
(2018)
Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni
eLife 7:e33221.
https://doi.org/10.7554/eLife.33221

Share this article

https://doi.org/10.7554/eLife.33221

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