New source of heart stem cells ...(lifornia San Diego. Using a different ge...)

Pu and Zhou showed that a specific population of cells in the epicardium, marked by Wt1 expression, not only differentiated into cardiomyocytes, but also smooth muscle cells, endothelial cells and fibroblasts (found in connective tissue).

"If you're going to regenerate a tissue, you need to regenerate the whole tissue, not just the cardiomyocytes," said Pu. "This progenitor population contains all the potential to regenerate multiple tissue types within the heart."

In recent years, the scientific literature has described many progenitors for cardiomyocytes, Pu added, but the markers used frequently did not play a direct role in heart development. For example, Sca-1 and c-Kit are markers that most stem cells express throughout the body, with no cardiac or developmental specificity.

"I think our best chance of getting a cell to do what we want is to modify what it was designed to do," Pu elaborated. "Some of these other progenitors were isolated in the adult heart, but we don't know what they do in the normal heart, and what they're related to in the embryo. However, we clearly know what progenitors expressing Wt1, Nkx2-5, and Isl1 do in the fetus: they can make fibroblasts, blood vessels, and cardiomyocytes. Therefore we think we have a good shot, in the adult heart, of recapitulating these events."

Pu considers his and Zhou's discovery to be a fortunate accident. They were trying, instead, to study a different gene, GATA4, by deleting it in the epicardium. "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. "Unexpectedly, we saw that these epicardial cells were becoming cardiomyocytesit was a l
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