The team used microarray technology to determine which genes were "playing" in embryonic endothelium to generate blood stem and progenitor cells and found that in the absence of Scl, the genes required for making cardiomyocytes were activated instead, said study co-first author Ben Van Handel, a post-doctoral fellow.
The lone difference was that Scl was missing in the process that resulted in the fate switch between blood and heart.
"Scl has a known role as a master regulator of blood development and when we removed it from the equation, no blood cells were made," Van Handel said. "That the removal of Scl resulted in fully functional cardiomyocytes in blood forming tissues was unprecedented."
The team used the yolk sac the first tissue where blood cells are made - from embryos that lacked Scl and within four hours of plating on the culture dish, the tissue had generated beating cardiomyocytes. The team also found similar cardiomyocyte potential in Scl-deficient embryos in the endocardium that lines the heart chambers. They also looked for genetic signatures that would suggest that these endothelial precursors could potentially also make other closely related tissues such as skeletal muscle, bone or kidney, but found no evidence of such plasticity. The default fate of the endothelium was to make cardiomyocytes in the absence of Scl, Mikkola said.
The findings may also have implications in cell reprogramming, which generally calls for adding factors to induce cell fate change, a process that can be problematic. It might be safer to suppress a factor like Scl to nudge cells into a cardiomyocyte fate, Mikkola said.
"This study opens new ways to think about what could be a potential source of cardiac stem cells," she said. "We now have a better understanding of how cardiac progenitor cells can be made and regulated, and this may one day lead us to a way to treat heart attacks by creating new he
|Contact: Kim Irwin|
University of California - Los Angeles Health Sciences