Using an enzyme called Cre recombinase, Pu and Zhou labeled epicardial cells in live mouse embryos with red fluorescent protein (RFP). Each time the Wt1 gene in these cells was activated, RFP lit up. Since the marker is inherited by descendants of the Wt1-expressing cell, the researchers could identify these descendants by looking for RFP.
"If the marker shows up in a cardiomyocyte, then I know that cardiomyocyte came from the Cre-expressing progenitor," said Pu.
At the moment, scientists are still trying to figure out whether and how the Wt1-expressing progenitors relate to the progenitors reported in 2006.
"What we think is that very early on, our particular progenitor expresses Nkx2-5 and Isl1, but quickly loses expression of both and starts expressing Wt1," said Pu. "Think of a lineage hierarchy with Nkx2-5 and Isl1 at the top, and Wt1 as a branch. These two lineages separate pretty early, before the heart is present in the embryo. However, the Wt1-expressing progenitor may retain some of the developmental capabilities of the progenitors expressing Nkx2-5 and Isl1."
Pu and Zhou now want to know whether the epicardium in an adult mouse could be induced to make cardiomyocytes. "If so, obviously this would be much more translatable to human studies," Pu said. Other ongoing questions are whether this newly-discovered progenitor is truly multipotent (able to turn into all other cell types), how multipotency is controlled, and whether this can be used therapeutically to benefit adults with heart failure.
The fact that the Wt1-expressing progenitors can also differentiate into fibroblasts in the developing heart suggests that they can contribute to scar formation in the adult heart after injury, Pu added. "But if we can turn the progenitors away from making scars, and instead turn them towards making cardiomyocytes, that would be pretty exciting."
Put another way, Pu and Zhou would
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| Contact: Bess Andrews Elizabeth.Andrews@childrens.harvard.edu 617-919-3110 Children's Hospital Boston Source:Eurekalert |