# PDGFRalpha+ fibroblast-like cells contribute to cardiac excitability

> **NIH NIH P20** · UNIVERSITY OF NEVADA RENO · 2021 · $209,741

## Abstract

Project Summary
Recent studies have identified a novel “fibroblast-like” cell in several organs that express the receptor tyrosine
kinase, PDGFRa (platelet-derived growth factor receptor-a). Using a mouse strain (Pdgfratm11(EGFP)Sor/J) in which
PDGFRα+ cells are constitutively labeled by expression of a transgene encoding a histone 2B-eGFP fusion
protein driven by the endogenous, cell-specific promoter for Pdgfra, we are able to isolate, purify, and study the
function and phenotype of fibroblast-like cells from a variety of organs, including the heart. We have
demonstrated that these cells are excitable and respond to agonists with rapid activation of large ionic currents.
We have further confirmed that the eGFP reporter is exclusive to PDGFRa+ cells by immunodetection using
antibodies against PDGFRα, thus definitively establishing these fibroblast-like cells as PDGFRα+ cells. In
preliminary studies for this proposal, we found that PDGFRα+ cells are widely distributed in cardiac muscles,
especially in sinoatrial nodal (SAN) and atrial tissues. A significant population of PDGFRa+ cells expresses the
classical fibroblast marker, vimentin, and the same population is labeled by PDGFRa antibodies in the primate
heart, indicating that this population corresponds to the cardiac fibroblast-like cells (CFCs) of the heart. Using
the eGFP reporter, we isolated and purified cardiac PDGFRa+ cells by FACS from SAN and atrial tissues. Our
subsequent characterization of PDGFRa+ cells in the SAN revealed that these cells are excitable and are capable
of generating spontaneous pacemaker activity through activation of a nonselective cation channel (NSCC).
Notably, we found that these cells form gap junctions with neighboring myocytes. Further investigation of the
automaticity of PDGFRa+ cells and more extensive characterization of the phenotypes of these cells will be
pursued in two Specific Aims: 1) Determine the genetic transcript signature of cardiac PDGFRα+ cells that
determine this cellular phenotype. 2) Determine the role(s) of NSCCs in generating spontaneous inward currents
in PDGFRα+ CFCs and in modulating cardiac AP waveform. Novel insights provided by successful completion
of this research proposal will facilitate a better understanding of the automaticity and phenotype of PDGFRa+
CFCs in SAN and atrial tissues and may support the development of novel therapeutic targets for pacemaker
deficiencies.

## Key facts

- **NIH application ID:** 10077908
- **Project number:** 5P20GM130459-03
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Haifeng Zheng
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $209,741
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077908

## Citation

> US National Institutes of Health, RePORTER application 10077908, PDGFRalpha+ fibroblast-like cells contribute to cardiac excitability (5P20GM130459-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10077908. Licensed CC0.

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