Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart

Nature. 2008 Jul 3;454(7200):109-13. doi: 10.1038/nature07060. Epub 2008 Jun 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage*
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heart / embryology*
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Mice
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Pericardium / cytology*
  • Pericardium / embryology
  • Pericardium / metabolism
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Transcription Factors
  • WT1 Proteins
  • Green Fluorescent Proteins