Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites

Abstract

Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of Migration-Coupled-DNA-Damage (MCDD) are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represent an unappreciated source of damage, that could be a significant source of mutations in animals during development or during long term tissue homeostasis.

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All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Sounak Sahu

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Divya Sridhar

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Prasad Abnave

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Noboyoshi Kosaka

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Anish Dattani

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. James M Thompson

    CRUK/MRC Oxford Institute for Radiation Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Mark A Hill

    CRUK/MRC Oxford Institute for Radiation Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Aziz Aboobaker

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    For correspondence
    aziz.aboobaker@zoo.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4902-5797

Funding

Medical Research Council (MR/M000133/1)

  • Aziz Aboobaker

Biotechnology and Biological Sciences Research Council (BB/K007564/1)

  • Aziz Aboobaker

University of Oxford, Clarendon Scholarship (N/A)

  • Sounak Sahu

University of Oxford, Natural Motion Scholarship (N/A)

  • Divya Sridhar

Marie Sklodowska Curie Horsozon 2020 (N/A)

  • Noboyoshi Kosaka

Biotechnology and Biological Sciences Research Council (BB/J014427/1)

  • Anish Dattani

Medical Research Council (MC-PC-12004)

  • James M Thompson

Medical Research Council (MR/T028165/1)

  • Aziz Aboobaker

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

Reviewing Editor

  1. Dario Riccardo Valenzano, Max Planck Institute for Biology of Ageing, Germany

Publication history

  1. Received: October 7, 2020
  2. Accepted: April 22, 2021
  3. Accepted Manuscript published: April 23, 2021 (version 1)
  4. Version of Record published: May 7, 2021 (version 2)

Copyright

© 2021, Sahu 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. Sounak Sahu
  2. Divya Sridhar
  3. Prasad Abnave
  4. Noboyoshi Kosaka
  5. Anish Dattani
  6. James M Thompson
  7. Mark A Hill
  8. Aziz Aboobaker
(2021)
Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites
eLife 10:e63779.
https://doi.org/10.7554/eLife.63779