# Patterning myocardial specification of human pluripotent stem cells

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $611,869

## Abstract

Project Summary/Abstract
Human pluripotent stem cells (hPSCs) originate from either embryonic or transcription factor-induced origins.
Under controlled conditions, they recapitulate cardiac development in vitro and give rise to cardiac myocytes of
all subtypes. The de novo cardiac myocytes are the best surrogate for human cardiomyocytes for drug
discovery, cardiotoxicity screen and cardiac cell replacement therapies. However, present technology for
deriving cardiac myocytes from hPSCs has major hurdles to clear toward the stated translational goals. One
major problem is heterogeneity; in a given batch, the derived cardiac myocytes are an indiscriminate blend of
all major subtypes of cardiomyocytes, i.e., nodal, atrial and ventricular. No cell therapy, toxicity screen and
drug discovery can afford to have undefined sub-populations of cardiac myocytes in a dish. We propose to
solve this problem by imposing one of the most potent signals during cardiac development on cardiac myocyte
patterning during hPSC differentiation. We hypothesize that retinoic acid (RA) signaling steers hPSCs to
differentiate toward discrete populations of ventricular or atrial cardiomyocytes of the first heart field. Our
preliminary data indicate that temporal and dose dependent manipulation of RA signaling leads to enriched
populations of atrial or ventricular cardiomyocytes from hESCs and hiPSCs. Furthermore, the cardiac
chamber-specific cardiomyocytes are functionally distinguishable in their electrical excitation and mechanical
contraction. We will build on our initial observations to discover a robust and generalizable signaling axis to
attain cardiac chamber-specific myocytes with genotypic and phenotypic hallmarks of the native ventricular and
atrial myocytes. Successful completion of this proposal will lead to understanding of female vs. male
differences in cardiogenic potential of hiPS cells and the fidelity of cardiac chamber-specific disease modeling.

## Key facts

- **NIH application ID:** 9906268
- **Project number:** 5R01HL143065-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Hee Cheol Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,869
- **Award type:** 5
- **Project period:** 2019-04-05 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906268

## Citation

> US National Institutes of Health, RePORTER application 9906268, Patterning myocardial specification of human pluripotent stem cells (5R01HL143065-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9906268. Licensed CC0.

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