# Regulatory mechanisms of adult cardiomyocyte proliferation

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $433,582

## Abstract

Project Summary
The ability to produce new myocytes within the heart would revolutionize our ability to treat cardiovascular
disease, and new strategies for generating new cardiac muscle cells (cardiomyocytes) after injury, such as
myocardial infarction (MI), are needed. Adult mammalian cardiomyocytes (CM) are generally considered to
be post-mitotic, hence previous nongenetic strategies to stimulate resident CM proliferation have to date
been insufficient to overcome CM loss with injury. However, recent reports demonstrate that adult
differentiated CMs in humans and mice have the ability to proliferate, albeit at low frequency, suggesting
that these rare events could be harnessed at a larger scale if the underlying mechanisms were fully
understood. Developmental studies show that the transcription factor Tbx20 promotes CM proliferation in
the fetal and neonatal heart. Tbx20 overexpression (Tbx20OE) in adult CMs induces fetal-like
characteristics, including proliferation, smaller size, mononucleation, and fetal contractile protein
expression. We hypothesize that induction of adult CM proliferation via a Tbx20-dependent pathway
requires both partial dedifferentiation, mediated by increased BMP signaling, and repression of cell cycle
inhibitors, including Btg2. The Aims are: 1) Determine if transient or exogenous Tbx20 expression is
sufficient to promote adult CM proliferation and repair in vivo. 2) Determine if BMP signaling promotes CM
dedifferentiation necessary for induction of adult CM proliferation in vivo. 3) Determine if loss of cell cycle
inhibitors Btg1/2 promotes CM proliferation and repair after injury. The ability to induce resident adult
mammalian CMs to proliferate by physiologic reversion to a fetal-like state would be an important advance
in efforts to generate new myocardium after cardiac injury.

## Key facts

- **NIH application ID:** 9837474
- **Project number:** 5R01HL135848-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Katherine E Yutzey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,582
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837474

## Citation

> US National Institutes of Health, RePORTER application 9837474, Regulatory mechanisms of adult cardiomyocyte proliferation (5R01HL135848-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9837474. Licensed CC0.

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