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.
Zhou
Bin
B
Harvard Stem Cell Institute and Department of Cardiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Ma
Qing
Q
Rajagopal
Satish
S
Wu
Sean M
SM
Domian
Ibrahim
I
Rivera-Feliciano
José
J
Jiang
Dawei
D
von Gise
Alexander
A
Ikeda
Sadakatsu
S
Chien
Kenneth R
KR
Pu
William T
WT
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