title: Assessment of DNA synthesis in Islet-1⁺ cells in the adult murine heart.
abstract: BACKGROUND
  Islet-1 positive (Islet-1(+)) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1(+) cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart.
  
  
  RESULTS
  DNA synthesis was analyzed by the incorporation of tritiated thymidine ((3)H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of (3)H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1(+) cells. Whereas Islet(-) non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed.
  
  
  CONCLUSIONS
  Islet-1(+) cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: f.weinberger@uke.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Weinberger
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: dennis.mehrkens@uk-koeln.de.
authors.forename: Dennis
authors.initials: D
authors.lastname: Mehrkens
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: starbatty@uke.uni-hamburg.de.
authors.forename: Jutta
authors.initials: J
authors.lastname: Starbatty
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: Philipp.Nicol@gmx.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Nicol
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Martinistr. 52, 20246 Hamburg, Germany. Electronic address: t.eschenhagen@uke.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
mesh_terms: D000818:Animals; D001345:Autoradiography; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004261:DNA Replication; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology*; D012849:Sinoatrial Node / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology*; D013936:Thymidine / Q000737:chemistry; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001616:beta-Galactosidase; D013936:Thymidine
keywords: Cardiac regeneration; Cell cycle; Sinoatrial node