# Characterization of hapln1a positive cells during zebrafish heart regeneration

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $480,023

## Abstract

Project Summary
Humans, like all mammals, possess a limited natural ability to efficiently replace lost myocardium with new
contractile tissue. This deficiency contributes to heart failure, the leading cause of morbidity and mortality in the
United States. By contrast, teleost fish robustly restore lost cardiac tissues after heart damage. Heart
regeneration in its natural context builds muscle by the proliferation of existing cardiomyocytes (CMs), facilitated
by the influences of non-muscle cells like the epicardium, which is a mesothelial layer that envelops the outer
surface of the heart and has important contributions to cardiac repair. However, the epicardium itself is a
heterogeneous tissue and which subpopulations offer benefits to regeneration events is far from clear.
 Our study reveals that a particular subset of epicardial cells with hapln1a expression has the strongest
association with regeneration. hapln1a+ epicardial cells first emerge in the ventricle base at the early juvenile
stage, when they associate with and sponsor regions of active CM expansion, events which direct maturation of
the ventricular wall during morphogenesis and restore lost myocardium during adult heart regeneration. Our
preliminary work further indicates that hapln1a+ cells pre-lead and guide coronary extensions during heart
morphogenesis and regeneration. Our single-cell RNA sequencing (scRNA-seq) analyses of hapln1a+ cells from
juvenile, adult uninjured, and regenerating hearts indicates that these cells are still heterogenous with different
functional clusters. We speculate that hapln1a+ cells can be genetically separated into subsets that are
specifically responsible for CM proliferation and coronary guidance, respectively. Our goal in this proposal is to
identify specific hapln1a+ cell clusters to pursue cell populations for therapeutic strategies. Our overall hypothesis
is that tcf21+ cell derived hapln1a+ cells have different clusters controlling myocardial expansion and coronary
guidance, a process in which has1 and serpine1 play critical roles in regulating extracellular matrix. To test this
hypothesis, we have created a panel of new zebrafish transgenic lines and mutants. We will define hapln1a+ cell
dynamism and related regulators, identify hapln1a+ cell clusters for CM proliferation and coronary guidance, and
the underlying molecular players. Our work will generate paradigm-shifting discoveries in cardiovascular biology.
These studies will reveal the impact of epicardial subsets on heart regeneration and identify key cellular and
molecular players in myocardial regeneration and coronary revascularization. These findings will potentially lead
to new therapeutic strategies like augmenting hapln1a+ cells and subpopulations to enhance the limited
regeneration displayed by humans after myocardial infarction.

## Key facts

- **NIH application ID:** 10882115
- **Project number:** 2R01HL142762-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jinhu Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $480,023
- **Award type:** 2
- **Project period:** 2018-09-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882115

## Citation

> US National Institutes of Health, RePORTER application 10882115, Characterization of hapln1a positive cells during zebrafish heart regeneration (2R01HL142762-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10882115. Licensed CC0.

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