Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium |
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Authors: | Zhou Bin von Gise Alexander Ma Qing Rivera-Feliciano José Pu William T |
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Institution: | a Harvard Stem Cell Institute and Department of Cardiology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA b Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA c Clinic of Neonatology, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany |
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Abstract: | Correct delineation of the hierarchy of cardiac progenitors is a key step to understanding heart development, and will pave the way for future use of cardiac progenitors in the treatment of heart disease. Multipotent Nkx2-5 and Isl1 cardiac progenitors contribute to cardiomyocyte, smooth muscle, and endothelial lineages, which constitute the major lineages of the heart. Recently, progenitors located within the proepicardium and epicardium were reported to differentiate into cardiomyocytes, as well as smooth muscle and endothelial cells. However, the relationship of these proepicardial progenitors to the previously described Nkx2-5 and Isl1 cardiac progenitors is incompletely understood. To address this question, we performed in vivo Cre-loxP-based lineage tracing. Both Nkx2-5- and Isl1-expressing progenitors contributed to the proepicardium and expressed Wt1 and Tbx18, markers of proepicardial progenitor cells. Interestingly, Nkx2-5 knockout resulted in abnormal proepicardial development and decreased expression of Wt1, suggesting a functional role for Nkx2-5 in proepicardium formation. Taken together, these results suggest that Nkx2-5 and/or Isl1 cardiac progenitors contribute to proepicardium during heart development. |
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Keywords: | Cardiac progenitor Proepicardium Heart development |
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