# Recording the cellular origins of cardiac regeneration

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $70,494

## Abstract

Project Summary
Human hearts fail to regenerate after injury, instead replacing injured regions of muscular myocardium with rigid
scar tissue that impairs cardiac output. Promoting the proliferation of cardiomyocytes (CMs) to replenish injured
heart muscle represents a promising strategy for improving the quality of life and preventing premature death of
patients recovering from myocardial infarction. Attempts at regenerative therapies have thus far failed to promote
meaningful restoration of lost myocardium. A promising source of therapeutic strategies involves the study of
vertebrates with the inherent ability to regenerate cardiac tissue, including the zebrafish model organism. Studies
comparing the cardiac injury response in non-regenerating mammals to zebrafish are made difficult, however,
by vast evolutionary divergence. More evolutionarily relevant comparisons are therefore needed to determine
the cellular behaviors that differentiate regenerating and non-regenerating species. This proposal describes
experiments aimed at identifying the unique genetic and cellular features that facilitate cardiac regeneration in
zebrafish through comparisons with medaka, a non-regenerating teleost fish species. In the first aim of this
fellowship proposal, I will generate organ-wide cell atlases of cardiac injury response in zebrafish and medaka
over several time points through single-cell RNA sequencing. Analyses of these datasets will reveal how key cell
types differ in their gene expression patterns in regenerating and non-regenerating species. In the second aim,
I utilize a recently developed single-cell lineage tracing technique to reconstruct the lineage relationships of cells
participating in cardiac regeneration in zebrafish. These experiments will provide a comprehensive view of which
CMs and immune cells are activated to restore injured tissue. In the final aim, I will test the hypothesis that the
cell-autonomous behaviors of responding immune cells facilitate cardiac regeneration in zebrafish. I will assay
heart regeneration following reciprocal transplantations of hematopoietic stem cells between zebrafish and
medaka, revealing whether immune cell functions are sufficient to impart regenerative potential. Together, these
experiments will provide important steps toward identifying the exact cell populations and gene expression
patterns that mediate cardiac regeneration and have the potential to aid in the development of targeted therapies
that promote cardiac regeneration in humans.

## Key facts

- **NIH application ID:** 10157709
- **Project number:** 1F32HL156644-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Clayton Carey
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,494
- **Award type:** 1
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10157709

## Citation

> US National Institutes of Health, RePORTER application 10157709, Recording the cellular origins of cardiac regeneration (1F32HL156644-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10157709. Licensed CC0.

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