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Updated: May 8, 2026
Generation of First Heart Field-like Cardiac Progenitors and Ventricular-like Cardiomyocytes from Human Pluripotent Stem Cells
Published on: June 19, 2018
A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells
Daniela Später1, Monika K Abramczuk, Kristina Buac
11] Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA.
Insights
Researchers identified Hcn4 as a specific marker for the first heart field (FHF). This discovery aids in understanding how cardiac muscle develops from FHF progenitors, crucial for heart formation.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Molecular Cardiology
Background:
- Mammalian heart development involves mesodermal progenitors from the first and second heart fields (FHF and SHF).
- The FHF forms the left ventricle and atria, while the SHF forms the right ventricle and outflow tract.
- Lack of exclusive markers has hindered detailed FHF progenitor studies.
Purpose of the Study:
- To identify a specific molecular marker for FHF progenitors.
- To characterize the contribution of FHF progenitors to cardiac development.
- To isolate cardiomyogenic progenitors from human embryonic stem cells.
Main Methods:
- Utilized Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as a potential FHF marker.
- Employed lineage tracing to track Hcn4+/FHF cells.
- Isolated cardiomyogenic progenitors using HCN4 as a surface marker in human embryonic stem cells.
Main Results:
- Hcn4 was validated as a specific marker for FHF progenitors.
- Lineage tracing confirmed Hcn4+/FHF cells contribute to FHF-derived cardiac structures.
- An early cardiomyogenic progenitor pool was identified within Hcn4+/FHF cells.
- HCN4 enabled the isolation of cardiomyogenic progenitors from human embryonic stem cells.
Conclusions:
- Hcn4 serves as a reliable marker for FHF progenitors.
- The FHF primarily generates cardiac muscle for the primitive heart tube's contractile activity.
- SHF progenitors are more involved in the diversification of heart cell lineages.
Abstract:
Most of the mammalian heart is formed from mesodermal progenitors in the first and second heart fields (FHF and SHF), whereby the FHF gives rise to the left ventricle and parts of the atria and the SHF to the right ventricle, outflow tract and parts of the atria. Whereas SHF progenitors have been characterized in detail, using specific molecular markers, comprehensive studies on the FHF have been hampered by the lack of exclusive markers. Here, we present Hcn4 (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker. Lineage-traced Hcn4+/FHF cells delineate FHF-derived structures in the heart and primarily contribute to cardiomyogenic cell lineages, thereby identifying an early cardiomyogenic progenitor pool. As a surface marker, HCN4 also allowed the isolation of cardiomyogenic Hcn4+/FHF progenitors from human embryonic stem cells. We conclude that a primary purpose of the FHF is to generate cardiac muscle and support the contractile activity of the primitive heart tube, whereas SHF-derived progenitors contribute to heart cell lineage diversification.
