# Dissecting epicardial contributions to zebrafish heart regeneration at the single-cell level

> **NIH NIH F31** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $46,752

## Abstract

Abstract
After an injury, such as myocardial infarction (MI), the adult human heart possesses only minimal
regenerative capabilities. In contrast to humans and most mammals, the adult zebrafish possesses a
remarkable ability to resolve fibrotic scarring and regenerate cardiac muscle after injury. Since there are
currently no clinical regenerative therapies for MI-induced injuries, there persists a great need in the
biomedical research community to understand the pro-regenerative machinery that enable robust
zebrafish heart regeneration. Indispensable to this regenerative process is the epicardium, which is the
outermost tissue layer of the heart. By contributing key paracrine signals and pro-regenerative cell types,
the epicardium promotes cardiomyocyte (CM) proliferation and revascularization of the injury site. That
being said, the precise mechanisms of these molecular and cellular processes are largely unknown, thus
raising many questions in regard to the regulation of zebrafish heart regeneration. To address these
questions, we performed single-cell RNA sequencing of isolated epicardial cells from injured and
uninjured adult zebrafish hearts. Preliminary analysis identified an adult epicardial progenitor cell
subpopulation that has the potential to differentiate into perivascular cells to facilitate angiogenesis. Here,
through genetic ablation and lineage tracing, we aim to determine the cellular and molecular contributions
of these progenitors to heart regeneration. Further analysis suggests that the Tgfb pathway regulates the
proliferation and differentiation of these epicardial progenitors. To gain a greater understanding of the
underlying regulatory mechanisms, we will further define the regenerative role of the Tgfb pathway in the
epicardium using genetic gain/loss-of function assays and modified RNA injections. In sum, this project
may ultimately inform strategies to target the pro-regenerative potential of epicardial progenitors to
improve heart repair and function in MI patients.

## Key facts

- **NIH application ID:** 10387801
- **Project number:** 1F31HL158168-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Sierra Kristen Duca
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387801

## Citation

> US National Institutes of Health, RePORTER application 10387801, Dissecting epicardial contributions to zebrafish heart regeneration at the single-cell level (1F31HL158168-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387801. Licensed CC0.

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