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Epitenon-derived progenitor cells in tendon healing and adaptation

Award Number: R00AR080757
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Epitenon-derived progenitor cells in tendon healing and adaptation - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $268,790 )
2025	2025	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	4	6/2/2025	NON-COMPETING CONTINUATION	$241,530
2025	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	11/19/2024	EXTENSION WITH OR WITHOUT FUNDS	$27,260
														Subtotal = $268,790

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	UNIVERSITY OF ROCHESTER	910 GENESEE ST	ROCHESTER	NY	14611	MONROE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/16/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $517,790

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Epitenon-derived progenitor cells in tendon healing and adaptation

Award Number: R00AR080757

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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