Heart Muscle Cells Made By Embryonic Blood Vessels That Produce Blood Stem Cells

"It was absolutely unbelievable," said Dr. Hanna Mikkola, associate professor of molecular, cell and developmental biology in the UCLA Life Sciences Division.. "These findings went beyond anything that we could have imagined. 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."

In other words, the lack of a single transcription factor — a type of gene that controls cell fate by regulating other genes — allows precursor cells in the endothelium that normally generate blood stem cells and blood progenitor cells in blood-forming tissues to become something else entirely: 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 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, a postdoctoral fellow at UCLA.

"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 shouldn't be playing."

"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," said Ben Van Handel, also a UCLA postdoctoral fellow.

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 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.

Adapted from the UCLA announcement.<