Islet-1 Cells Are Cardiac Progenitors Present During the Entire Lifespan: From the Embryonic Stage to Adulthood

The aim of this study was to longitudinally characterize the distribution of cells actively expressing the progenitor transcription factor islet-1 (Isl1(+)) during the embryonic life, the postnatal period, and adulthood. In this study, we have used direct immunohistochemical staining toward the protein Isl1 in a longitudinal rat model. Cells actively expressing Isl1 were traced in embryos from gestational day (GD) 11 until adulthood. In early cardiac development (GD 11), the Isl1(+) progenitors were located in a greater abundance in the paracardiac regions, areas suggested to be the second heart field. To a lesser extent, Isl1(+) cells were present within the bulbotruncal region and the truncus arteriosus. During the following days until GD 15, the Isl1(+) cells were mainly observed at the proximal outflow tract (OFT) and at the inflow area of the right atrium. No Isl1(+) cells were detected in the left ventricle. Compared with GD 11, more Isl1(+) cells seemed to co-express cardiomyocyte markers and a minority of the Isl1(+) cells was undifferentiated. Unexpectedly, only few undifferentiated Isl1(+) cells were Ki67(+) while a lot of TnT(+) cardiomyocytes were proliferating in the ventricles. After birth, immature Isl1(+) cells were still present in the OFT where they resided until adulthood. Our data suggest that during embryogenesis, Isl1(+) cells migrate from extracardiac regions into the proximal part of the heart, proliferating and giving rise to cardioblasts. Unexpectedly, only a minority of the Isl1(+) cells while a majority of ventricular cardiomyocytes were proliferating. The Isl1(+) cell pool persists into adulthood, which might open up new strategies to repair damaged myocardium.