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

Daniela Später; Monika K. Abramczuk; Kristina Buac; Lior Zangi; Maxine W. Stachel; Jonathan Clarke; Makoto Sahara; Andreas Ludwig; Kenneth R. Chien

doi:10.1038/ncb2824

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

Daniela Später, Monika K. Abramczuk, Kristina Buac, Lior Zangi, Maxine W. Stachel, Jonathan Clarke, Makoto Sahara, Andreas Ludwig, Kenneth R. Chien

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

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^1-3. Whereas SHF progenitors have been characterized in detail, using specific molecular markers^4-8, 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.

Original language	English
Pages (from-to)	1098-1106
Number of pages	9
Journal	Nature Cell Biology
Volume	15
Issue number	9
DOIs	https://doi.org/10.1038/ncb2824
State	Published - Sep 2013
Externally published	Yes

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

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 atria1-3. Whereas SHF progenitors have been characterized in detail, using specific molecular markers4-8, 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.",

author = "Daniela Sp{\"a}ter and Abramczuk, {Monika K.} and Kristina Buac and Lior Zangi and Stachel, {Maxine W.} and Jonathan Clarke and Makoto Sahara and Andreas Ludwig and Chien, {Kenneth R.}",

note = "Funding Information: assistance with electrophysiology recordings, L. Bu for technical advice, K. Buac, E. Hansson, C. Riedel and L. Bu for critical reading of the manuscript and discussions, and C. Hartmann for advice on double-fluorescence in situ hybridizations. D.S. has received a D.F.G. (German Research Foundation) postdoctoral fellowship. K.B. was supported by a NHLBI T32HL007208 grant. This work is financially supported by the NIH U01 HL098 166 and NIH U01H100408 research grants.",

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AU - Abramczuk, Monika K.

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AU - Stachel, Maxine W.

AU - Clarke, Jonathan

AU - Sahara, Makoto

AU - Ludwig, Andreas

AU - Chien, Kenneth R.

N1 - Funding Information: assistance with electrophysiology recordings, L. Bu for technical advice, K. Buac, E. Hansson, C. Riedel and L. Bu for critical reading of the manuscript and discussions, and C. Hartmann for advice on double-fluorescence in situ hybridizations. D.S. has received a D.F.G. (German Research Foundation) postdoctoral fellowship. K.B. was supported by a NHLBI T32HL007208 grant. This work is financially supported by the NIH U01 HL098 166 and NIH U01H100408 research grants.

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N2 - 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 atria1-3. Whereas SHF progenitors have been characterized in detail, using specific molecular markers4-8, 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.

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

Abstract

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