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Replicative Potential of Muscle Stem Cells

Award Number: R01AR070360
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: 08/17/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Replicative Potential of Muscle Stem Cells - Project Summary Skeletal muscle tissue is maintained and can be dynamically modeled to fit ongoing needs by changes in muscular activity. Myofibers, the primary cells that comprise the contractile elements of skeletal muscle, are post-mitotic and maintained by a pool of stem cells, termed satellite cells, which are localized to a niche be- tween the myofiber and overlying basal lamina. Loss of mobility arising from loss of skeletal muscle function occurs following an injury, is an inevitable consequence of aging and a consequence of many neuromuscular diseases, the latter two resulting in reduced quality of life and increased morbidity, requiring hospitalization or home care, significantly raising health care costs. These complex physiological changes are well documented but the mechanisms responsible for these changes are not understood. SCs (satellite cells) maintain muscle throughout life, providing a constant source of new myonuclei that appears to occur primarily by asymmetric division. Loss of SC asymmetric division contributes to age-related losses of SC function during aging and to the dystrophic muscle phenotype. Enhancing the ability of SCs to di- vide asymmetrically improves strength in aged muscle and improves dystrophic muscle function. The depend- ence of skeletal muscle health on SC maintenance, which in turn requires SCs divide asymmetrically empha- sizes an essential role for SC asymmetric division that has not been adequately addressed. EGFR (epidermal growth factor receptor) and FGFR1 signaling promote SCs to divide asymmetrically, identifying these as two critical signaling pathways involved in maintaining SCs. Activation of EGFR signaling improves dystrophic muscle phenotypes and activation of FGFR1 signaling in SCs from aged muscle rescues asymmetric division restoring SC numbers to youthful levels and increases strength in aged mice, suggesting that SC asymmetric division is essential to maintain skeletal muscle health. The primary premise for the proposed experiments in this application is that driving SCs to divide asymmetrically improves muscle health. However, SCs comprise a minor population of cells within skeletal muscle (1-3%) and thus, how can improvement of SC health affect an entire muscle? To fulfill this knowledge gap, we plan to identify the pathways driving SCs to divide asymmetri- cally and elucidate the mechanisms by which stimulation of SC asymmetric division enhances skeletal muscle function.


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 = $492,082 )
2025	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	6/11/2025	NON-COMPETING CONTINUATION	$492,082
														Subtotal = $492,082

Issue Date FY: 2024 ( Subtotal = $492,082 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	6/25/2024	NON-COMPETING CONTINUATION	$492,082
														Subtotal = $492,082

Issue Date FY: 2023 ( Subtotal = $507,300 )
2023	2023	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	7	8/1/2023	NON-COMPETING CONTINUATION	$507,300
2023	2022	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	6	5/8/2023	COMPETING CONTINUATION	$0
2023	2021	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	5/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $507,300

Issue Date FY: 2022 ( Subtotal = $527,386 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	8/17/2022	COMPETING CONTINUATION	$527,386
														Subtotal = $527,386

Issue Date FY: 2021 ( Subtotal = $328,636 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5	7/21/2021	NON-COMPETING CONTINUATION	$328,636
														Subtotal = $328,636

Issue Date FY: 2020 ( Subtotal = $338,800 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	7/30/2020	NON-COMPETING CONTINUATION	$338,800
														Subtotal = $338,800

Issue Date FY: 2019 ( Subtotal = $338,800 )
2019	2019	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	7/26/2019	NON-COMPETING CONTINUATION	$338,800
														Subtotal = $338,800

Issue Date FY: 2018 ( Subtotal = $338,800 )
2018	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST STE 481 572 UCB	BOULDER	CO	80309	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	8/29/2018	NON-COMPETING CONTINUATION	$338,800
														Subtotal = $338,800

Issue Date FY: 2017 ( Subtotal = $338,800 )
2017	2017	REGENTS OF THE UNIVERSITY OF COLORADO, THE	3100 MARINE ST., RM 479 572 UCB	BOULDER	CO	80303	BOULDER	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/26/2017	NEW	$338,800
														Subtotal = $338,800

Grand Total All Awards = $3,702,686

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Replicative Potential of Muscle Stem Cells

Award Number: R01AR070360

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: 08/17/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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