Featured Research

from universities, journals, and other organizations

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

Date:
August 2, 2012
Source:
University of California - Los Angeles Health Sciences
Summary:
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.

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

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.


Story Source:

The above story is based on materials provided by University of California - Los Angeles Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ben Van Handel, Amélie Montel-Hagen, Rajkumar Sasidharan, Haruko Nakano, Roberto Ferrari, Cornelis J. Boogerd, Johann Schredelseker, Yanling Wang, Sean Hunter, Tõnis Org, Jian Zhou, Xinmin Li, Matteo Pellegrini, Jau-Nian Chen, Stuart H. Orkin, Siavash K. Kurdistani, Sylvia M. Evans, Atsushi Nakano, Hanna K.A. Mikkola. Scl Represses Cardiomyogenesis in Prospective Hemogenic Endothelium and Endocardium. Cell, 2012; 150 (3): 590 DOI: 10.1016/j.cell.2012.06.026

Cite This Page:

University of California - Los Angeles Health Sciences. "Embryonic blood vessels that make blood stem cells can also make beating heart muscles." ScienceDaily. ScienceDaily, 2 August 2012. <www.sciencedaily.com/releases/2012/08/120802122613.htm>.
University of California - Los Angeles Health Sciences. (2012, August 2). Embryonic blood vessels that make blood stem cells can also make beating heart muscles. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2012/08/120802122613.htm
University of California - Los Angeles Health Sciences. "Embryonic blood vessels that make blood stem cells can also make beating heart muscles." ScienceDaily. www.sciencedaily.com/releases/2012/08/120802122613.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) — Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) — A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) — More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins