Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart.
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.
Harvard Stem Cell Institute and Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Bin
B
Zhou
Qing
Q
Ma
Satish
S
Rajagopal
Sean M
SM
Wu
Ibrahim
I
Domian
José
J
Rivera-Feliciano
Dawei
D
Jiang
Alexander
A
von Gise
Sadakatsu
S
Ikeda
Kenneth R
KR
Chien
William T
WT
Pu
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010496:Pericardium / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D014157:Transcription Factors; D025721:WT1 Proteins; D049452:Green Fluorescent Proteins