PUBLICATION
Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration
- Authors
- Anderson, T., Mo, J., Gagarin, E., Sherwood, D., Blumenkrantz, M., Mao, E., Leon, G., Levitz, H., Chen, H.J., Tseng, K.C., Fabian, P., Crump, J.G., Smeeton, J.
- ID
- ZDB-PUB-231002-61
- Date
- 2023
- Source
- NPJ Regenerative medicine 8: 5151 (Journal)
- Registered Authors
- Crump, Gage DeKoeyer, Smeeton, Joanna
- Keywords
- none
- Datasets
- GEO:GSE224197
- MeSH Terms
- none
- PubMed
- 37726321 Full text @ NPJ Regen Med
Citation
Anderson, T., Mo, J., Gagarin, E., Sherwood, D., Blumenkrantz, M., Mao, E., Leon, G., Levitz, H., Chen, H.J., Tseng, K.C., Fabian, P., Crump, J.G., Smeeton, J. (2023) Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration. NPJ Regenerative medicine. 8:5151.
Abstract
After traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding gene legumain. Analysis of legumain mutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping