# Epitenon-derived progenitor cells in tendon healing and adaptation

> **NIH NIH R00** · UNIVERSITY OF ROCHESTER · 2024 · $249,000

## Abstract

Project Summary
Though thought to serve many important functions in overall tendon function, including facilitating both healing
and adaptation to mechanical load, the true identity and function of the epitenon has remained elusive due to a
lack of genetic markers that specifically target epitenon cells. In preliminary studies, we identified a novel
population of GLAST-lineage (GLASTu') cells in the epitenon that contribute to both tendon healing following
acute injury and tendon adaptation in response to mechanical overload by differentiating into scleraxis (Scx)expressing
tenocytes. Identification of a genetic marker for epitenon cells as well as demonstration of their
capacity for tenogenic differentiation has opened an exciting new avenue of tendon research with the long-term
goal of understanding the role that epitenon cells play in regulating overall tendon homeostasis and to identify
ways to leverage epitenon cell behavior to improve tendon health. During the K99 phase of this award, we
established voluntary wheel running as a tool for modeling adaptive tendon growth in mice and generated
numerous sophisticated genetic mouse models to facilitate the study of how GLASTu" epitenon progenitors and
Sex-expressing tenocytes coordinate to affect tissue-level adaptation. To further explore this relationship during
R00 phase of this award, the proposed studies build on our prior work to test the central hypothesis that GLAS Tu"
epitenon cells are an indispensable source of tenogenic progenitor cells for tendon adaptation and that signaling
between epitenon cells and tenocytes is critical for the tenogenic response of GLASTLic progenitors. Combining
genetic lineage tracing with integrated spatial/single-cell RNA-sequencing, we will create a comprehensive
spatial and temporal atlas that defines the pathways regulating the coordinated mechanoresponse of epitenon
cells, tenocytes, and GLASTu" progenitor cells (Aim 1A), To mechanistically test the hypothesis that coordination
between epitenon cells and tenocytes is required for the proper tendon adaptive response to load, we will
inducibly deplete either epitenon cells or tenocytes prior to tendon load in complementary experiments (Aim 1 B)
and assess how disruption of GLASTu, epitenon cell/tenocyte communication affects the overall tendon adaptive
response. Collectively, these data will provide the first comprehensive characterization of epitenon cells and their
function in tendon biology.

## Key facts

- **NIH application ID:** 11077382
- **Project number:** 4R00AR080757-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Anne E.C. Nichols
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11077382

## Citation

> US National Institutes of Health, RePORTER application 11077382, Epitenon-derived progenitor cells in tendon healing and adaptation (4R00AR080757-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11077382. Licensed CC0.

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