The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging

Zamboulis, Danae E ORCID: 0000-0003-2839-7620, Marr, Neil, Lenzi, Luca, Birch, Helen L, Screen, Hazel RC, Clegg, Peter D and Thorpe, Chavaunne T (2024) The Interfascicular Matrix of Energy Storing Tendons Houses Heterogenous Cell Populations Disproportionately Affected by Aging. AGING AND DISEASE, 15 (1). pp. 295-310.

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Official URL: http://dx.doi.org/10.14336/ad.2023.0425-1

Abstract

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to injury, with incidence increasing with aging, peaking in the 5<sup>th</sup> decade of life in the human Achilles tendon. The interfascicular matrix (IFM), which binds tendon fascicles, plays a key role in energy storing tendon mechanics, and aging alterations to the IFM negatively impact tendon function. While the mechanical role of the IFM in tendon function is well-established, the biological role of IFM-resident cell populations remains to be elucidated. Therefore, the aim of this study was to identify IFM-resident cell populations and establish how these populations are affected by aging. Cells from young and old SDFTs were subjected to single cell RNA-sequencing, and immunolabelling for markers of each resulting population used to localise cell clusters. Eleven cell clusters were identified, including tenocytes, endothelial cells, mural cells, and immune cells. One tenocyte cluster localised to the fascicular matrix, whereas nine clusters localised to the IFM. Interfascicular tenocytes and mural cells were preferentially affected by aging, with differential expression of genes related to senescence, dysregulated proteostasis and inflammation. This is the first study to establish heterogeneity in IFM cell populations, and to identify age-related alterations specific to IFM-localised cells.

Item Type:	Article
Uncontrolled Keywords:	interfascicular matrix, proteostasis, senescence, single cell sequencing, tendon aging, tendon cell populations
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	20 Feb 2024 11:29
Last Modified:	20 Feb 2024 11:29
DOI:	10.14336/AD.2023.0425-1
Open Access URL:	https://doi.org/10.14336/AD.2023.0425-1
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178821