Embryonic blood vessels that make blood stem cells can also make beating heart muscles

August 2, 2012

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 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 for use in regenerative medicine, said study senior author Dr. Hanna Mikkola, an associate professor of molecular, cell and in Life Sciences and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and at UCLA.

"It was absolutely unbelievable. These findings went beyond anything that we could have imagined," Mikkola said. "The in the embryonic that normally gives rise to can generate 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.

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. Credit: Hanna Mikkola Lab, University of California - Los Angeles Health Sciences

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 shouldn't 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."

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 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 to replace those that were damaged."

Going forward, Mikkola and her team plan to investigate the developmental and regenerative potential of the -derived cardiac , and define the mechanisms by which Scl can at the same time activate one fate while suppressing another.

"These results call for future studies to examine the prospect of harnessing the latent cardiogenic potential in the vasculature for use in regenerative medicine, and to investigate whether similar development plasticity exists in other major cell fate decisions in the developing embryo," the study states.

Explore further: Scientists identify crucial cell and signaling pathway in placental blood stem cell niche

Related Stories

Scientists identify crucial cell and signaling pathway in placental blood stem cell niche

March 1, 2012
(Medical Xpress) -- UCLA stem-cell researchers have identified a certain type of cell and a signaling pathway in the placental niche that play a key role in stopping blood stem cells from differentiating into mature blood ...

Recommended for you

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.