Navigation Links
Embryonic blood vessels that make blood stem cells can also make beating heart muscles
Date:8/2/2012

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 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 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 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 heart muscle cells to replace those that were damaged."

Going forward, Mikkola and her team plan to investigate the developmental and regenerative potential of the endothelium-derived cardiac progenitor cells, 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.


'/>"/>
Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles Health Sciences
Source:Eurekalert  

Related biology news :

1. Researchers identify mechanisms that allow embryonic stem cells to become any cell in the human body
2. Amniotic fluid yields alternatives to embryonic stem cells
3. Magical state of embryonic stem cells may help overcome hurdles to therapeutics
4. Navigating the Patent Minefield of Embryonic Stem Cell Product Development; Free Kindle Fire Tablet and Research Database with Purchase
5. New York Stem Cell Foundation scientist grows bone from human embryonic stem cells
6. Navigating the IP Minefield of Human Embryonic Stem Cell Development
7. BU researchers derive purified lung and thyroid progenitors from embryonic stem cells
8. Embryonic development protein active in cancer growth
9. Key function of protein discovered for obtaining blood stem cells as source for transplants
10. Blood sugar diabetes risk for South Asians
11. Blood vessel forming potential of stem cells from human placenta and umbilical cord blood
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Embryonic blood vessels that make blood stem cells can also make beating heart muscles
(Date:1/18/2016)... 2016  Extenua Inc., a pioneering developer of ... and access of ubiquitous on-premise and cloud storage, today ... Cyber.  ... C4ISR and Cyber initiatives in support of National ... technology solutions," said Steve Visconti , Extenua ...
(Date:1/13/2016)... , January 13, 2016 ... the addition of the  "India Biometrics ... & Forecast (2015-2020)"  report to ... ) has announced the addition of ... Market - Estimation & Forecast (2015-2020)" ...
(Date:1/8/2016)... MANCHESTER, United Kingdom , Jan. 8, 2016   ... diagnostic products, today announced the closing of a $9 million ... Proceeds from the financing will be used to accelerate the ... for detecting early-stage pressure ulcers. United ... receiving CE Mark approval. The device,s introduction has been met ...
Breaking Biology News(10 mins):
(Date:2/9/2016)... Feb. 9, 2016  DNAtrix, a clinical ... cancer, announced that its lead product, DNX-2401, ... as an orphan medicinal product for the ... of glioma, strikes approximately 25,000 people a ... http://photos.prnewswire.com/prnh/20160208/330986LOGO --> ...
(Date:2/9/2016)... , Feb. 9, 2016 ... Inhibitors-Pipeline Insights, 2016", report provides in depth ... development activities around the Protein-Tyrosine Phosphatase 1B ... product profiles in various stages of development ... II, Phase III and Preregistration. Report covers ...
(Date:2/8/2016)... 2016 Novan, Inc. today announced that Director Robert ... Directors of Novan. In addition, Robert Keegan has been ... Carolina . --> North Carolina ... received a total of $32.8 million of net proceeds in a ... network originating throughout the Research Triangle area of North ...
(Date:2/8/2016)... , ... February 08, 2016 , ... ... and leading supplier of Semantic Graph Database technology, today announced the availability of ... of Cloudera Enterprise through the Cloudera Certified Technology Program (CCPT). AllegroGraph ...
Breaking Biology Technology: