Epitenon-derived progenitors drive fibrosis and regeneration after flexor tendon injury in a spatially-dependent manner

Anne E. C. Nichols (), Lauren Benoodt, Emmanuella Adjei-Sowah, Kyle Jerreld, Alexander Kollar, Constantinos Ketonis and Alayna E. Loiselle
Additional contact information
Anne E. C. Nichols: University of Rochester Medical Center
Lauren Benoodt: University of Rochester School of Medicine and Dentistry
Emmanuella Adjei-Sowah: University of Rochester Medical Center
Kyle Jerreld: University of Rochester Medical Center
Alexander Kollar: University of Rochester Medical Center
Constantinos Ketonis: University of Rochester Medical Center
Alayna E. Loiselle: University of Rochester Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Flexor tendon injuries are common and heal poorly owing to both the deposition of function-limiting peritendinous scar tissue and insufficient healing of the tendon itself. Therapeutic options are limited due to a lack of understanding of the cell populations that contribute to these processes. Here, we identified the epitenon as a major source of cells that contribute to both peritendinous fibrosis and regenerative tendon healing following acute tendon injury. Using a combination of genetic lineage tracing and single cell RNA-sequencing (scRNA-seq), we profiled the behavior and contributions of each cell fate to the healing process in a spatio-temporal manner. Integrated scRNA-seq analysis of mouse healing with human peritendinous scar tissue revealed remarkable transcriptional similarity between mouse epitenon-derived cells and fibroblasts present in human peritendinous scar tissue, which was further validated by immunofluorescent staining for conserved markers. Finally, ablation of pro-fibrotic epitenon-derived cells post-tendon injury significantly improved functional recovery. Combined, these results clearly identify the epitenon as the cellular origin of an important progenitor cell population that could be leveraged to improve tendon healing.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60704-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60704-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60704-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().