# Defining key differences in mouse fibroblasts during digit regeneration and fibrosis

> **NIH NIH F31** · HARVARD UNIVERSITY · 2024 · $36,110

## Abstract

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.

## Key facts

- **NIH application ID:** 10878695
- **Project number:** 5F31AR082220-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Vivian Jou
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $36,110
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-05-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10878695

## Citation

> US National Institutes of Health, RePORTER application 10878695, Defining key differences in mouse fibroblasts during digit regeneration and fibrosis (5F31AR082220-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10878695. Licensed CC0.

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