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Epicardial cell type identified as cardiomyocyte progenitors
23 June 2008
Medwire News: Scientists have identified a novel group of epicardial stem cells that can differentiate into cardiomyocytes.
William Pu (Harvard Medical School, Boston, Massachusetts, USA) and colleagues report in the journal Nature that a subset of epicardial cardiogenic precursors expressing the transcription factor Wt1, and originating in the epicardium, differentiate into fully functional cardiomyocytes in mice.
The team made the surprise discovery while studying another transcription factor, GATA4, in epicardial cells. "The tool we created for that experiment irreversibly marks the cells involved, so you can see where their descendants are headed in normal development," Pu explained.
Pu and colleagues found that Wt1 was expressed in the pro-epicardium and epicardium, but not myocardium, in embryonic mice. Wt1 was expressed predominantly in pro-epicardium and in scattered pericardial cells at embryonic day (E) 9.5, becoming confined to the epicardium at E15.5.
The researchers used recombinant gene technology to induce heritable expression of two reporter genes, encoding β-galactosidase (β-gal) and red fluorescent protein (RFP), in the Wt1-expressing cells and so analyze their fate during development of the murine heart.
Whereas the Wt1-expressing progenitors were confined to the epicardium at E15.5, their descendants (Wt1-derived cells), expressing β-gal and RFP, were present in a mosaic pattern throughout the myocardium and mostly adopted a smooth muscle cell fate, with a minority becoming endothelial cells.
But the researchers also found that some Wt1-derived cells differentiated into cardiomyocytes, as demonstrated by co-expression of the marker proteins troponin T2 and sarcomeric actinin.
Further analysis suggested that the Wt1-expressing pro-epicardial cells share the same origin as previously identified multipotent cardiac progenitors expressing the genes Nkx2-5 and Isl1.
"These experiments have identified a previously unrecognized cardiomyocyte progenitor population in the developing heart that may be of use for cardiac regeneration or repair," the authors conclude.
