UCLA stem cell researchers have discovered a surprising and unexpected phenomenon in the embryonic endothelium, the thin layer of cells lining the interior of blood vessels, where blood stem cells are made during early development.
The scientists found that 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.
"It was absolutely unbelievable," said Dr. Hanna Mikkola, the study's senior author. "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."
The finding is important because it suggests that the endothelium can serve as a source of heart muscle cells. The research may provide a new understanding of how to make cardiac stem cells for use in regenerative medicine, said Mikkola, who is an associate professor of molecular, cell and developmental biology in the UCLA Life Sciences Division and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.
The two-year study is published Aug. 3 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, co-first author of the study and 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."
The team used microarray technology to determine which genes were "playing" in the 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 co-first study author Ben Van Handel, also a UCLA postdoctoral 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."