A current hope is that cardiac stem cells could one day be manipulated to rebuild cardiac tissue damaged by heart disease. Edward Morrisey and colleagues from the University of Pennsylvania address a fundamental question in the cardiac stem cell field, "What are the molecular pathways required for expansion and development of cardiac stem cells?"
The authors have delineated a novel and essential pathway for the expansion of recently identified islet (Isl-1)positive cardiac progenitor cells. These cells help form the right ventricle and outflow tract of the developing heart.
The authors show that Wnt signaling through activation of fibroblast growth factor 10 (FGF10) expression was required for expansion of Isl-1 cardiac progenitors in the anterior heart; loss of Wnt signaling lead to a loss of the right ventricle and defective development of the outflow tract while sparing the left sided structures of the heart. Isl-1 positive precursor cells with active Wnt signaling were fated to become outflow tract and right ventricular muscle cells.
Activation of Wnt signaling lead to increased numbers of Isl-1 positive progenitors, increased FGF10 expression, and increased outflow tract development. The direct relationship between Wnt and FGF10 signaling was demonstrated by the finding that FGF10 is a direct target of Wnt/beta-catenin signaling in cardiac development. These data identify a pathway by which the number and function of cardiac progenitor stem cells can be amplified, thus providing critical insight into the ability to harness these cells for future cardiac reparative therapies.
This study appears online on June 21 in advance of publication in the July print issue of the Journal of Clinical Investigation. The title of the article is "Wnt/beta-catenin signaling promotes expansion of Isl-1 positive cardiac progenitor cells through regulation of FGF signaling."
Materials provided by Journal of Clinical Investigation. Note: Content may be edited for style and length.
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