Ongoing repair of migration-coupled DNA damage allows planarian adult stem cells to reach wound sites.
cell migration
developmental biology
planarian
regeneration
stem cells
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
23 04 2021
23 04 2021
Historique:
received:
07
10
2020
accepted:
22
04
2021
pubmed:
24
4
2021
medline:
28
10
2021
entrez:
23
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33890575
doi: 10.7554/eLife.63779
pii: 63779
pmc: PMC8104965
doi:
pii:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MR/T028165/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K007564/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M000133/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U142760473
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J014427/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-PC-12004
Pays : United Kingdom
Informations de copyright
© 2021, Sahu et al.
Déclaration de conflit d'intérêts
SS, DS, PA, NK, AD, JT, MH, AA No competing interests declared
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