# Macrophage functional dynamics in adult heart regeneration

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $584,877

## Abstract

Much of the basic research on cardiac biology has been focused on cardiomyocytes (CMs), aiming to unravel
the basic principles underlying cardiac physiology and pathophysiology for future development of therapeutic
interventions to treat cardiac diseases. Besides CMs, the heart contains many other cell types including
endothelial cells, fibroblasts, and a wide variety of immune cells. During heart development and homeostasis,
non-myocytes (nonCMs) have been increasingly recognized to play active roles in regulating various CM
behaviors. Yet a lack of detailed information on the cellular identities and cell states of the nonCMs associated
development and homeostasis is a major hurdle to precisely delineating the biological events in heart
development and homeostasis. In our recently published study, we delineated nonCMs cellular and
transcriptomic dynamics during cardiac regeneration. Through scRNA-seq, we identified major nonCM cell types,
including multiple macrophage (MC), FB and EC subpopulations with unique tempo-spatial distribution.
Prticularly, we found that MC exists in multiple definable states that exhibit dynamic functional changes from
acute inflammatory response to inflammation resolution. Interestingly, perturbing MC function resulted in
defective cardiac regeneration. Combining Topologizer and RNA velocity analyses, we uncovered dynamic
transition between MC functional states and identified factors involved in mRNA processing and transcriptional
regulation associated with the transition. However, whether and how nonCMs interact at the subpopulation level,
and MC dynamic functional change affects nonCMs interactions and hence heart regeneration remains largely
unexplored. In this research proposal, we hypothesize that heart regeneration is a highly orchestrated process
involving temporally regulated MC function executed by the distinct subtypes and their interactions with other
nonCM cell types. To test this hypothesis, we aim to 1) define the role of the inflammatory MCs (iMCs) subtype
in nonCM interaction and heart regeneration, 2) delineate the role of the immune surveillance MC (isMCs)
subtype in nonCM interaction and heart regeneration, and 3) study the molecular mechanism governing
transition of MC functional states.

## Key facts

- **NIH application ID:** 10817085
- **Project number:** 5R01HL164933-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jiandong Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $584,877
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817085

## Citation

> US National Institutes of Health, RePORTER application 10817085, Macrophage functional dynamics in adult heart regeneration (5R01HL164933-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817085. Licensed CC0.

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