# Cellular plasticity and lineage in mammalian digit tip regeneration

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $539,305

## Abstract

PROJECT SUMMARY
Mice, monkeys, and humans can regenerate their digit tips following amputation. This innate form of composite
tissue regeneration is a highly coordinated process involving multiple tissue types interacting to form a
replacement digit tip with the proper composition and pattern. Defining what is unique to the digit tip in terms of
molecular signals or cell types, and how it relates to regeneration, can inform broader regeneration efforts of
non-regenerative tissues. One foothold into this process is the recent cellular characterization of the mouse
digit tip blastema, the collection of progenitor cells that forms following amputation that is necessary to give rise
to the regenerating tissue. Our single cell RNA sequencing-based analysis of the blastema identified 13
molecularly distinct fibroblast populations. With this, we now have specific cellular populations to individually
assess for their function(s) in digit tip regeneration. We propose that the subpopulations of fibroblasts in the
regenerating mouse digit tip encompass separable roles including progenitors, structural, and niche-factor-
producing cells, of which a subset may promote composite tissue regeneration. In this proposal, we focus on
digit tip fibroblast heterogeneity and aim to determine the origin, function, and regenerative potential of each of
these populations. We will analyze the spatial organization of the fibroblast subpopulations in mouse and
human digit tips and determine those comprised of progenitor cells. Using single cell RNA sequencing with
lineage tracing, we will determine when the digit tip heterogeneity of the adult digit is established, and define
the cellular plasticity and regenerative contribution of the fibroblast populations to the regenerated tissue.
Finally, we will investigate how the digit tip fibroblast subpopulations relate in identity and function to fibroblasts
from non-regenerative proximal amputations. Collectively, the data generated in this project will provide a
comprehensive understanding of the heterogeneous population of digit tip fibroblasts in the context of
regeneration, which will lay the foundation for composite tissue regeneration on a broader scale.

## Key facts

- **NIH application ID:** 10498196
- **Project number:** 1R01HD109200-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jessica A Lehoczky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $539,305
- **Award type:** 1
- **Project period:** 2022-08-03 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498196

## Citation

> US National Institutes of Health, RePORTER application 10498196, Cellular plasticity and lineage in mammalian digit tip regeneration (1R01HD109200-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498196. Licensed CC0.

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