Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart

Circ Res. 2012 May 11;110(10):1303-10. doi: 10.1161/CIRCRESAHA.111.259630. Epub 2012 Mar 15.


Rationale: 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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Aorta / cytology
  • Aorta / metabolism
  • Biomarkers / metabolism
  • Chromogenic Compounds
  • Galactosides
  • Indoles
  • LIM-Homeodomain Proteins / genetics*
  • LIM-Homeodomain Proteins / metabolism*
  • Lac Operon
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / metabolism
  • RNA, Messenger / metabolism
  • Sinoatrial Node / cytology
  • Sinoatrial Node / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • Biomarkers
  • Chromogenic Compounds
  • Galactosides
  • Indoles
  • LIM-Homeodomain Proteins
  • RNA, Messenger
  • Transcription Factors
  • insulin gene enhancer binding protein Isl-1
  • 5-bromo-4-chloro-3-indolyl beta-galactoside