Researchers defined the early lineage segregation during early mammalian heart development

August 25, 2014

The heart contains four different chambers and different cell types such as cardiomyocytes (CMs), endocardial cells (ECs) covering the inner layer of the heart, epicardial cells covering the outer layer of the heart and smooth muscle cells  (SMCs) covering the coronary arteries and main vessels. During embryonic development, the cells that will formed the heart need to be specified at the correct time, migrate at the correct place, proliferate to ensure the harmonious morphogenesis and growth of the heart. Any defects during this critical stage of development will lead to congenital heart diseases, which represent the first cause of severe birth malformations. While different progenitors that contribute to the development of the heart have been identified, it remains unclear whether these cells arise from common progenitors or derive from distinct progenitors that are specified at different time during development.

In a new study published in Nature Cell Biology, researchers led by Pr. Cédric Blanpain, MD/PhD, WELBIO investigator at the IRIBHM, Université libre de Bruxelles, Belgium, have identified temporally distinct populations of cardiac that differentiate into different cell lineages and contribute to different regions of the .

Fabienne Lescroart, Samira Chabab and colleagues performed for the first time a temporally controlled clonal analysis of early cardiac progenitors, in which they marked single at the early stages of embryonic and assess the contribution of single cardiac progenitors to the heart development. In contrast to the prevalent notion that these cells arise from a common progenitors, the researchers found that the different cardiac progenitors are specified at different time points during development and will only contribute to the morphogenesis of certain cardiac regions, like if the heart is build from different blocs that are made at different time during development. Furthermore, the researchers found that in contrast to the multilineage differentiation of these cells in vitro, the early population of cardiac progenitors did not differentiate into all cardiovascular lineages in vivo, but were rather pre-specified to give rise to either cardiac cells or endocardial cells, suggesting that the ultimate fate of the progenitors can be regulated by the environmental cues that the different progenitors encounter during cardiac morphogenesis. "We were extremely surprized to find that the early the cardiac progenitors have a much narrow regional contribution and were not able to differentiate into more than one cell types in contrast to late born cardiac progenitors. We need to completely rethink about the way heart is formed" comment Fabienne Lescroart, the first author of the study.

Using new tools to isolate for the first time the early cardiac progenitors during , Fabienne Lescroart, Samira Chabab and colleagues define the molecular characteristics of these different progenitors and showed that the different populations of Mesp1 progenitors, although very similar molecularly, present also notable difference, consistent with their lineage and regional contribution. In addition, characterization of the gene expression at a single cell level have shown that the cardiac progenitors were molecularly heterogenous and expressed different combination of genes that will define the cell fate and regionalization of each progenitors. Understanding how this specificity is achieved will be important to instruct and/or restrict the fate of multipotent cardiovascular progenitors into a particular cell lineage in vivo. The answers to these questions will be important to design new strategies to direct the differentiation of pluripotent cells and iPS cells specifically into pure population of , and for improving cellular therapy in cardiac diseases.

In conclusion, this work uncovers how the heart is build from temporally distinct progenitors with different differentiation potential. This work provides the first temporal clonal analysis of heart development and the first molecular characterization of cardiac progenitors at the early step of cardiac morphogenesis. " This new study really changes the way we think about cardiac development and have important implications for better understanding the aetology of congenital cardiac malformations and should be the starting point of further studies to understand how the regionalization and the choice of differentiation into a particular cardiovascular lineage is achieved, which have important implications for improving cell therapy during cardiac repair" comments Pr Cédric Blanpain, the senior author of this study.

Explore further: Study identifies molecules that guide embryonic heart-forming cells

More information: Fabienne Lescroart , et al. "Early lineage restriction in temporally distinct populations of Mesp1 progenitors during mammalian heart development." Nature Cell Biology 2014, DOI: 10.1038/ncb3024

Related Stories

Study identifies molecules that guide embryonic heart-forming cells

May 5, 2014
Scientists at the University of East Anglia have made an important step in understanding how hearts are formed in developing embryos.

Researchers find that coronary arteries hold heart-regenerating cells

August 20, 2014
Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

An attractive solution for heart repair

August 15, 2014
Stem cell therapy is a promising option for repairing heart tissue damaged by heart attack. However, the main obstacle to cardiac stem cell therapy also happens to be pretty difficult to get around – and that's the fact ...

Distinct chromatin patterns linked to heart development

September 17, 2012
(HealthDay)—Distinct chromatin patterns accompany the development of heart cells from embryonic cells, providing a blueprint that could help identify the causes of congenital heart disease, according to a study published ...

Common stem cell in heart and lung development explains adaption for life on land

July 21, 2013
The evolution of adaptations for life on land have long puzzled biologists – are feathers descendents of dinosaur scales, how did arms and legs evolve from fins, and from what ancient fish organ did the lung evolve?

Researchers identify stem cells responsible for tissue repair

September 4, 2012
The skin, which is an essential barrier that protects our body against the external environment, undergoes constant turnover throughout life to replace dead cells that are constantly sloughed off from the skin surface. During ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

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.