Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites
- University of Oxford, United Kingdom
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.
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Author details
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.
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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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
