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A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells

doi: 10.1038/ncb2824
pmid: 23974038
A HCN4+ cardiomyogenic progenitor derived from the first heart field and human pluripotent stem cells
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.
- Harvard University United States
- Karolinska Institute Sweden
- Massachusetts General Hospital United States
- University of Georgia Georgia
Pluripotent Stem Cells, Potassium Channels, Heart Ventricles, Myocardium, Cyclic Nucleotide-Gated Cation Channels, Gene Expression Regulation, Developmental, Muscle Proteins, Cell Differentiation, Embryo, Mammalian, Mesoderm, Mice, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Morphogenesis, Animals, Humans, Cell Lineage, Myocytes, Cardiac, Heart Atria, Biomarkers, Embryonic Stem Cells
Pluripotent Stem Cells, Potassium Channels, Heart Ventricles, Myocardium, Cyclic Nucleotide-Gated Cation Channels, Gene Expression Regulation, Developmental, Muscle Proteins, Cell Differentiation, Embryo, Mammalian, Mesoderm, Mice, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Morphogenesis, Animals, Humans, Cell Lineage, Myocytes, Cardiac, Heart Atria, Biomarkers, Embryonic Stem Cells
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