# Uncovering mechanisms and progenitors responsible for limb regeneration

> **NIH NIH F32** · HARVARD UNIVERSITY · 2020 · $67,446

## Abstract

PROJECT SUMMARY
Limb loss affects nearly 2 million Americans and comes with complications such as infection, pain, and blood
clots, in addition to serious psychological impact. Currently, the standard of care following limb loss is the use
of a prosthetic. The ideal response following limb loss would be the regeneration of an exact replicate of the
lost limb. This is not the response humans make, but other species such salamanders have the ability to
perfectly regenerate lost appendages. Therefore, understanding the remarkable ability of salamanders to
regenerate lost limbs may elucidate mechanisms to unlock the regenerative capacity of humans. Following
limb amputation salamanders form a structure called the blastema. The blastema is a pool of tissue specific
progenitor cells that are responsible for regenerating the lost limb. Recent gains in molecular biology has
allowed for discovery of genes that are enriched and specific to the regenerating limb. We have recently
identified von Willebrand Factor D and EGF domains (VWDE) as a highly blastema enriched and specific
gene. We hypothesize that the blastema contains a pool of transcriptionally distinct progenitor cells and pan-
blastemal genes, such as VWDE, support this niche. Our first aim will evaluate the role and functional domains
of VWDE in blastema cell function and mammalian cell differentiation. Our second aim will work to uncover
other progenitor cells (i.e. dermis, cartilage, Schwann cells) using single cell RNA-sequencing to elucidate the
cellular heterogeneity of the blastema. These studies will provide essential information on a novel gene and
work to uncover different progenitor cells required for limb regeneration in salamanders. These gains in
understanding of salamander limb regeneration will put us closer to unlocking the ability to promote
regeneration in humans.

## Key facts

- **NIH application ID:** 9989640
- **Project number:** 5F32HD092120-04
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Nicholas Leigh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-07-16 → 2021-07-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989640

## Citation

> US National Institutes of Health, RePORTER application 9989640, Uncovering mechanisms and progenitors responsible for limb regeneration (5F32HD092120-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989640. Licensed CC0.

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