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Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites
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 woun...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104965/ https://www.ncbi.nlm.nih.gov/pubmed/33890575 http://dx.doi.org/10.7554/eLife.63779 |
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author | Sahu, Sounak Sridhar, Divya Abnave, Prasad Kosaka, Noboyoshi Dattani, Anish Thompson, James M Hill, Mark A Aboobaker, Aziz |
author_facet | Sahu, Sounak Sridhar, Divya Abnave, Prasad Kosaka, Noboyoshi Dattani, Anish Thompson, James M Hill, Mark A Aboobaker, Aziz |
author_sort | Sahu, Sounak |
collection | PubMed |
description | 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 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 represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis. |
format | Online Article Text |
id | pubmed-8104965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-81049652021-05-11 Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites Sahu, Sounak Sridhar, Divya Abnave, Prasad Kosaka, Noboyoshi Dattani, Anish Thompson, James M Hill, Mark A Aboobaker, Aziz eLife Developmental Biology 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 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 represents an unappreciated source of damage, which could be a significant source of mutations in animals during development or during long-term tissue homeostasis. eLife Sciences Publications, Ltd 2021-04-23 /pmc/articles/PMC8104965/ /pubmed/33890575 http://dx.doi.org/10.7554/eLife.63779 Text en © 2021, Sahu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Sahu, Sounak Sridhar, Divya Abnave, Prasad Kosaka, Noboyoshi Dattani, Anish Thompson, James M Hill, Mark A Aboobaker, Aziz Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title | Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title_full | Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title_fullStr | Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title_full_unstemmed | Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title_short | Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites |
title_sort | ongoing repair of migration-coupled dna damage allows planarian adult stem cells to reach wound sites |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104965/ https://www.ncbi.nlm.nih.gov/pubmed/33890575 http://dx.doi.org/10.7554/eLife.63779 |
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