Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart

• Published in: Nature 2008-07, Vol.454 (7200), p.109-113
• Main Authors: Rajagopal, Satish, Ikeda, Sadakatsu, Ma, Qing, Rivera-Feliciano, José, von Gise, Alexander, Wu, Sean M, Domian, Ibrahim, Zhou, Bin, Jiang, Dawei, Pu, William T, Chien, Kenneth R
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; Fluorescence; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genetic aspects; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Heart; Heart - embryology; Heart cells; Homeobox Protein Nkx-2.5; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humanities and Social Sciences; Labeling; letter; Mice; Molecular and cellular biology; multidisciplinary; Myocytes, Cardiac - cytology; Myocytes, Cardiac - metabolism; Organogenesis; Pericardium - cytology; Pericardium - embryology; Pericardium - metabolism; Physiological aspects; Proteins; Science; Science (multidisciplinary); Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; WT1 Proteins - genetics; WT1 Proteins - metabolism
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature07060

The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium-an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1+ precursors differentiated into fully functional cardiomyocytes. Wt1+ proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5+ and Isl1+ progenitors. These results identify Wt1+ epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.