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Updated: Dec 30, 2025
Generation of First Heart Field-like Cardiac Progenitors and Ventricular-like Cardiomyocytes from Human Pluripotent Stem Cells
Published on: June 19, 2018
Pathogenic Potential of Hic1-Expressing Cardiac Stromal Progenitors
Hesham Soliman1, Ben Paylor2, R Wilder Scott2
1Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada; Faculty of Pharmaceutical Sciences, Minia University, Minia, Egypt.
Insights
Cardiac fibro/adipogenic progenitors (cFAPs) contribute to heart disease. Targeting cFAP activation may treat myocardial infarction and arrhythmogenic cardiomyopathy.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Regenerative Medicine
Background:
- The cardiac stroma harbors multipotent mesenchymal progenitors, but their lineage relationships are unclear.
- Cardiac fibro/adipogenic progenitors (cFAPs) are key mesenchymal cells in the heart.
- Understanding cFAP behavior is crucial for cardiac disease research.
Purpose of the Study:
- To identify and characterize cardiac stromal progenitor cells.
- To investigate the role of cFAPs in cardiac damage and disease.
- To explore therapeutic strategies targeting cFAP activity.
Main Methods:
- Identification of heart-resident PDGFRa+
- SCA-1+ cells as cFAPs.
- Assessment of cFAP response to ischemic damage.
- Pharmacological inhibition of cFAP differentiation.
- Lineage-specific gene deletion to activate cFAPs.
Main Results:
- cFAPs generate fibrogenic cells post-ischemic damage.
- Inhibition of cFAP differentiation reduces post-myocardial infarction remodeling and improves cardiac function.
- Activation of cFAPs in undamaged hearts causes fibrofatty infiltration and arrhythmogenic cardiomyopathy features.
Conclusions:
- cFAPs are critical progenitors in the cardiac stroma.
- Modulating cFAP activity offers a promising therapeutic avenue for diverse cardiac diseases.
- Targeting cFAPs could treat conditions ranging from myocardial infarction to arrhythmogenic cardiomyopathy.
Abstract:
The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identified heart-resident PDGFRa+ SCA-1+ cells as cardiac fibro/adipogenic progenitors (cFAPs) and show that they respond to ischemic damage by generating fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (post-MI) remodeling and leads to improvement in cardiac function. In the undamaged heart, activation of cFAPs through lineage-specific deletion of the gene encoding the quiescence-associated factor HIC1 reveals additional pathogenic potential, causing fibrofatty infiltration within the myocardium and driving major pathological features pathognomonic in arrhythmogenic cardiomyopathy (AC). In this regard, cFAPs contribute to multiple pathogenic cell types within cardiac tissue and therapeutic strategies aimed at modifying their activity are expected to have tremendous benefit for the treatment of diverse cardiac diseases.
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