# Single Cell Sequencing of Human iPSC-CM Subtype Identity and Function

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $692,649

## Abstract

PROJECT SUMMARY
Cardiomyocytes from human induced pluripotent stems cells (iPSC-CMs) possess the potential to study
patient-specific heart disease in a dish. Their usefulness ranges from being important in drug development,
cellular therapies, as well as understanding human cardiac development. Although we can generate beating
cardiomyocytes in a dish, their representation of human adult subtypes (e.g., atrial, ventricular, and nodal) is
still rudimentary. To understand the factors which regulate iPSC-CMs into various cardiomyocyte subtypes,
we will utilize a single cell RNA sequencing approach to identify critical transcription factors involved in the
transition of progenitor cardiomyocytes into an atrial-like (retinoic acid-treated cultures) or ventricular-like
(default differentiation parameters) phenotype. Furthermore, we will genetically engineer our iPSCs to be
deficient in or mark the expression of core subtype specific markers using CRISPR/Cas9 technology. In using
this approach, we will assess what are the master transcription factors involved in cardiomyocyte subtype
specification and whether a specific cardiomyocyte subpopulation formed in vitro is better at repairing the
damaged heart. In using a miniswine myocardial infarction model, we will assess how well subpopulations
integrate within the ischemic miniswine hearts as well as assess the functional recovery parameters that each
cardiomyocyte subpopulations will contribute to repairing the damaged myocardium. Finally, by recovering
the iPSC-CMs that have integrated within the heart, we will assess by single-cell sequencing how the
transcriptome of these cells changes after being functional in vivo. We anticipate that these studies will shed
light on how various subtypes can be differentiated in vitro which will further accelerate our use of iPSC-CMs
for research and therapeutic applications.

## Key facts

- **NIH application ID:** 9920771
- **Project number:** 5R01HL145676-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** THOMAS QUERTERMOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $692,649
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920771

## Citation

> US National Institutes of Health, RePORTER application 9920771, Single Cell Sequencing of Human iPSC-CM Subtype Identity and Function (5R01HL145676-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920771. Licensed CC0.

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