Localization of Islet-1–Positive Cells in the Healthy and Infarcted Adult Murine Heart
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 after myocardial infarction.
Methods and Results: Distribution of Islet-1+ cells in adult heart was investigated using transgenic 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, scattered within the wall of the great vessels, and a strictly delimited cluster between 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 β-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 heart.
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.
- Received October 25, 2011.
- Revision received March 7, 2012.
- Accepted March 8, 2012.
- © 2012 American Heart Association, Inc.