Newswise UCLA stem cell researchers have found for the first time a surprising and unexpected plasticity in the embryonic endothelium, the place where blood stem cells are made in early development.

Scientists found that the lack of one transcription factor, a type of gene that controls cell fate by regulating other genes, allows the precursors that normally generate blood stem and progenitor cells in blood forming tissues to become something very unexpected - beating cardiomyocytes, or heart muscle cells.

The finding is important because it suggests that the endothelium can serve as a source of heart muscle cells. The finding may provide new understanding of how to make cardiac stem cells for use in regenerative medicine, said study senior author Dr. Hanna Mikkola, an associate professor of molecular, cell and developmental biology in Life Sciences and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

It was absolutely unbelievable. These findings went beyond anything that we could have imagined, Mikkola said. The microenvironment in the embryonic vasculature that normally gives rise to blood cells can generate cardiac cells when only one factor, Scl, is removed, essentially converting a hematopoietic organ into a cardiogenic organ.

The two-year study is published Aug. 3, 2012 in the peer-reviewed journal Cell.

The findings were so surprising, in fact, that Mikkola and her team did not want to believe the results until all subsequent assays proved the finding to be true, said Amelie Montel-Hagen, study co-first author and a post-doctoral fellow.

To make sure we had not switched the samples between blood forming tissues and the heart we ran the experiments again and repeatedly got the same results, Montel-Hagen said. It turns out Scl acts as a conductor in the orchestra, telling the other genes in the endothelium who should be playing and who shouldnt be playing.

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.

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Embryonic Blood Vessels that Make Blood Stem Cells can also Become Beating Heart Muscle Cells