title: Islet-1 cells are cardiac progenitors present during the entire lifespan: from the embryonic stage to adulthood.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Rami
authors.initials: R
authors.lastname: Genead
authors.forename: Christian
authors.initials: C
authors.lastname: Danielsson
authors.forename: Agneta B
authors.initials: AB
authors.lastname: Andersson
authors.forename: Matthias
authors.initials: M
authors.lastname: Corbascio
authors.forename: Anders
authors.initials: A
authors.lastname: Franco-Cereceda
authors.forename: Christer
authors.initials: C
authors.lastname: Sylvén
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Grinnemo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology* / Q000254:growth & development*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1