title: Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart.
abstract: BACKGROUND
  The transcription factor Islet-1 is a marker of cardiovascular progenitors during embryogenesis. The isolation of Islet-1-positive (Islet-1(+)) cells from early postnatal hearts suggested that Islet-1 also marks cardiac progenitors in adult life.
  
  
  OBJECTIVE
  We investigated the distribution and identity of Islet-1(+) cells in adult murine heart and evaluated whether their number or distribution change with age or after myocardial infarction.
  
  
  RESULTS
  Distribution of Islet-1(+) cells in adult heart was investigated using gene targeted mice with nuclear β-galactosidase inserted into the Islet-1 locus. nLacZ-positive cells were only present in 3 regions of the adult heart: clusters in the interatrial septum and around the pulmonary veins, scattered within the wall of the great vessels, and a strictly delimited cluster between the right atrium and superior vena cava. Islet-1(+) cells in the first type of clusters coexpressed markers for parasympathetic neurons. Positive cells in the great arteries coexpressed smooth muscle actin and myosin heavy chain, indicating a smooth muscle cell identity. Very few Islet-1(+) cells within the outflow tract expressed the cardiomyocyte marker α-actinin. Islet-1(+) cells in the right atrium coexpressed the sinoatrial node pacemaker cell marker HCN4. Cell number and localization remained unchanged between 1 to 18 months of age. Consistently Islet-1 mRNA was detected in human sinoatrial node. Islet-1(+) cells could not be detected in the infarct zone 2 to 28 days after myocardial infarction, aside from 10 questionable cells in 1/13 hearts.
  
  
  CONCLUSIONS
  Our results identify Islet-1 as a novel marker of the adult sinoatrial node and do not provide evidence for Islet-1(+) cells to serve as cardiac progenitors.
authors.affiliation: Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Weinberger
authors.forename: Dennis
authors.initials: D
authors.lastname: Mehrkens
authors.forename: Felix W
authors.initials: FW
authors.lastname: Friedrich
authors.forename: Mandy
authors.initials: M
authors.lastname: Stubbendorff
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Hua
authors.forename: Jana Christina
authors.initials: JC
authors.lastname: Müller
authors.forename: Sonja
authors.initials: S
authors.lastname: Schrepfer
authors.forename: Sylvia M
authors.initials: SM
authors.lastname: Evans
authors.forename: Lucie
authors.initials: L
authors.lastname: Carrier
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
mesh_terms: D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002863:Chromogenic Compounds; D005697:Galactosides; D007211:Indoles; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D007763:Lac Operon; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D002863:Chromogenic Compounds; D005697:Galactosides; D007211:Indoles; D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside