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 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.
authors: 1] 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.
authors: Daniela
authors: D
authors: Später
authors: Monika K
authors: MK
authors: Abramczuk
authors: Kristina
authors: K
authors: Buac
authors: Lior
authors: L
authors: Zangi
authors: Maxine W
authors: MW
authors: Stachel
authors: Jonathan
authors: J
authors: Clarke
authors: Makoto
authors: M
authors: Sahara
authors: Andreas
authors: A
authors: Ludwig
authors: Kenneth R
authors: KR
authors: Chien
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D015221:Potassium Channels
chemical_list: D015415:Biomarkers; D054815:Cyclic Nucleotide-Gated Cation Channels; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels
references: Heart. 2009 Jun;95(12):960-3
references: 19033293
references: Nat Neurosci. 2010 Jan;13(1):133-40
references: 20023653
references: Dev Biol. 2008 Nov 1;323(1):98-104
references: 18775691
references: Dev Cell. 2011 Sep 13;21(3):394-409
references: 21920310
references: Development. 2008 Jan;135(2):193-205
references: 18156162
references: Nature. 2005 Feb 10;433(7026):647-53
references: 15703750
references: Cell. 2006 Dec 15;127(6):1151-65
references: 17123592
references: Nature. 2008 Jul 3;454(7200):109-13
references: 18568026
references: Development. 2011 Nov;138(21):4777-87
references: 21989917
references: Science. 2009 Oct 16;326(5951):426-9
references: 19833966
references: Cell. 2003 Apr 18;113(2):235-48
references: 12705871
references: Dev Biol. 2005 Nov 1;287(1):134-45
references: 16188249
references: Circ Res. 2010 Jul 9;107(1):153-61
references: 20466980
references: Cell Res. 2013 Oct;23(10):1172-86
references: 24018375
references: Cell Stem Cell. 2007 Aug 16;1(2):165-79
references: 18371348
references: Nature. 2009 Jul 2;460(7251):113-7
references: 19571884
references: Dev Cell. 2003 Dec;5(6):877-89
references: 14667410
references: Heart Rhythm. 2011 Aug;8(8):1254-63
references: 21421080
references: J Mol Cell Cardiol. 2008 Jul;45(1):62-9
references: 18538341
references: Curr Top Dev Biol. 2010;90:1-41
references: 20691846
references: Ann N Y Acad Sci. 2010 Feb;1188:15-24
references: 20201881
references: Dev Cell. 2012 Aug 14;23(2):280-91
references: 22898775
references: Circ Res. 2009 Jun 5;104(11):1267-74
references: 19423846
references: Cell. 2007 Mar 9;128(5):947-59
references: 17350578
references: Dev Biol. 2007 Apr 1;304(1):286-96
references: 17258700
references: J Histochem Cytochem. 1967 Oct;15(10):580-8
references: 4863647
references: Dev Biol. 1999 Jul 1;211(1):100-8
references: 10373308
references: Science. 2013 May 10;340(6133):744-8
references: 23519212
references: J Mol Cell Cardiol. 2011 Dec;51(6):997-1006
references: 21945247
references: Cardiovasc Res. 2003 May 1;58(2):399-409
references: 12757874
references: Nature. 2008 Jul 3;454(7200):104-8
references: 18480752
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: Dev Biol. 2010 Dec 1;348(1):97-106
references: 20883686
references: Development. 2000 Apr;127(8):1607-16
references: 10725237
references: Int J Dev Biol. 2002;46(4):431-9
references: 12141429
references: Gene Expr Patterns. 2003 Dec;3(6):777-83
references: 14643687
references: Cardiovasc Res. 2010 Jul 1;87(1):92-101
references: 20110338
references: Dev Cell. 2012 Mar 13;22(3):639-50
references: 22421048
references: Cell Stem Cell. 2008 Apr 10;2(4):320-31
references: 18397752
references: Heart. 2010 Jul;96(14):1154-61
references: 20610462
references: Development. 1997 Oct;124(19):3895-908
references: 9367445