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Defining key differences in mouse fibroblasts during digit regeneration and fibrosis

Award Number: F31AR082220
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 05/29/2025

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Defining key differences in mouse fibroblasts during digit regeneration and fibrosis - PROJECT SUMMARY Composite tissue regeneration is very limited in mammals; however, humans and mice can fully regenerate the distal tips of the digits following amputation. This process involves the formation of a blastema, a cellular structure that is the source of the regenerated tissue and is integral to successful regeneration. Proximal amputations beyond the nail do not form a blastema and result in fibrotic wound-healing. This differential behavior makes the mouse digit tip an ideal model system to investigate the cellular and molecular factors driving each wound-healing response and why complex regeneration is so limited in mammals. Specifically, this project will focus on fibroblast subtypes and their role in fibrosis versus regeneration. Fibroblasts are a major contributor to the blastema and play an integral part in fibrosis; thus, they may be a cell population that drives the decision between fibrosis and regeneration. Our single cell transcriptomic (scRNA-seq) analysis of the regenerating blastema revealed an extremely heterogenous fibroblast population and that the subpopulations had distinct population dynamics and lineage trajectories during blastema formation and maturation. I hypothesize that there are specific fibroblast subtypes that promote regeneration, inhibit fibrosis, or both. However, no studies have performed direct lineage contributions by tracing fibroblast subpopulations in regeneration and fibrosis. Additionally, the in vivo functional roles and importance of our computationally defined candidate pro-regenerative genes have not been established. This project will utilize single-cell CRISPR based DNA barcoding for lineage tracing fibroblasts at the subtype resolution (Aim 1) and plasmid electroporation for gene delivery to functionally assess candidate pro-regenerative genes (Aim 2). Together, my two aims will provide important insight into how the fibrotic and regenerative processes are determined in the mouse digit tip and will open additional avenues for more effective clinical treatments for large wounds or amputations in humans.


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: 2026 ( Subtotal = -$2,500 )
2026	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	12/2/2025	NON-COMPETING CONTINUATION	-$2,500
														Subtotal = -$2,500

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	9/15/2025	NON-COMPETING CONTINUATION	$0
2025	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	5/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $38,610 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	6/18/2024	NON-COMPETING CONTINUATION	$38,610
														Subtotal = $38,610

Issue Date FY: 2023 ( Subtotal = $37,166 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	1	5/15/2023	NEW	$0
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE 5TH FL	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	5/15/2023	NEW	$37,166
														Subtotal = $37,166

Grand Total All Awards = $73,276

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Defining key differences in mouse fibroblasts during digit regeneration and fibrosis

Award Number: F31AR082220

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 05/29/2025

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