(Press-News.org) PHILADELPHIA – 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?
Biologists have known that the co-development of the cardiovascular and pulmonary systems is a recent evolutionary adaption to life outside of water, coupling the function of the heart with the gas exchange function of the lung. And, the lung is one of the most recent organs to have evolved in mammals and is arguably the most vital for terrestrial life.
The coordinated maturation of the cells of these two systems is illustrated during embryonic development, when the primitive lung progenitor cells protrude into the primitive cardiac progenitor cells as the two organs develop in parallel to form the cardiopulmonary circulation. However, little is known about the molecular cues guiding this simultaneous development, and how a common progenitor cell for both organs may influence the pathology of such related diseases as pulmonary hypertension.
In a new paper published this week online in Nature, a team from the Perelman School of Medicine, University of Pennsylvania, shows that the pulmonary vasculature, the blood vessels that connect the heart to the lung, develops even in the absence of the lung. Mice in which lung development is inhibited still have pulmonary blood vessels, which revealed to the researchers that cardiac progenitors, or stem cells, are essential for cardiopulmonary co-development.
The Penn team, led by Edward E. Morrisey, PhD, professor of Medicine and Cell and Developmental Biology and scientific director of the Penn Institute for Regenerative Medicine, identified a population of multi-potent CardioPulmonary mesoderm Progenitor cells they named CPPs. The CPPs can be distinguished from many other early embryonic cells by the expression of a well-studied signaling molecule Wnt2.
"We asked if these progenitor cells are capable of generating both heart and lung derivatives," says Morrisey. "Our data show that Wnt2-positive cells exist prior to lung development and help coordinate lung and heart co-development by generating cell types in both tissues."
The issue of how the lung develops and connects to the cardiovascular system has intrigued the Morrisey lab for many years. "It's pretty obvious to anyone who has looked at the anatomy of most terrestrial animals that the heart and lung are intimately linked. This is even reflected in clinical medicine where in many places, including the Perelman School of Medicine, the Division of Cardiovascular Medicine was once referred to as the Division of Cardiopulmonary Medicine," notes Morrisey.
The Morrisey lab began with a couple of simple questions: how do the lung and heart co-develop and what are the critical signals that regulate this process? The breakthrough in this work occurred when the team characterized the expression pattern of the Wnt2 gene.
"Wnt2 is expressed in a unique place in the early embryo -- exactly in between the early heart and foregut tube, where the lung will arise from." This allowed the researchers to create a model system in mice, whose cardiopulmonary anatomy is very similar to humans, and ask whether Wnt2-positive cells could coordinate heart and lung co-development.
Using cell lineage tracing analysis, they showed that Wnt2 cells generate single clones that, in turn, generate both heart and lung tissue, including cardiomyocytes and blood vessel cells such as vascular smooth muscle. Indeed, CPPs are capable of generating the vast majority of early embryonic cell types in the heart and lung. These studies also showed that the different cell lineages within the lung are related. For example, vascular smooth muscle and airway smooth muscle share a common progenitor cell in the lung.
The development of CPPs is regulated by the expression of another well-known protein called hedgehog, which is required for proper connection of the pulmonary vasculature to the heart. These studies show that hedgehog, which is also expressed by early lung progenitor cells, helps to promote CPPs to differentiate into the smooth muscle component of the pulmonary vasculature.
Together, these studies identify a novel population of multi-potent cardiopulmonary progenitors that coordinate heart and lung co-development, which is required for adaptation to terrestrial existence.
The finding that CPPs coordinate lung and heart co-development also has important implications for diseases that affect both organs, such as pulmonary hypertension. It is unclear whether pulmonary hypertension is primarily a lung disease or whether there are also intrinsic defects in the heart or cardiovascular system. The identification of CPPs could provide important insight into pulmonary hypertension and other diseases by identifying a common progenitor cell for both organs. Future studies will focus on whether CPPs exist in the adult cardiopulmonary system and whether they play a role in the response of the lung and heart to injury or disease.
INFORMATION:
Co-authors are Tien Peng, Ying Tian, Cornelis J. Boogerd, Min Min Lu, Rachel S. Kadzik, Kathleen M. Stewart, all from Penn, and Sylvia M. Evans, University of California, San Diego.
This work was funded by the Heart, Lung and Blood Institute (HL110942, HL100405, HL087825, HL117649) and the American Heart Association Jon DeHaan Myogenesis Center.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.
Common stem cell in heart and lung development explains adaption for life on land
2013-07-22
ELSE PRESS RELEASES FROM THIS DATE:
A flip of the mitotic spindle has disastrous consequences for epithelial cells
2013-07-22
VIDEO:
Stowers investigators use genetics and live cell imaging to illuminate molecular mechanisms that position the cell division machinery in growing tissues.
Click here for more information.
KANSAS CITY, MO—Constructing a body is like building a house—if you compromise structural integrity, the edifice can collapse. Nowhere is that clearer on a cellular level than in the case of epithelial sheets, single layers of cells that line every body cavity from the gut to mammary ...
Current efforts will not save the world's most endangered cat
2013-07-22
Almost 100 million euros has been spent so far on conservation efforts for the last 250 remaining Iberian lynxes in the wild. But the charismatic species is likely to go extinct within 50 years because the current management plans do not account for the effects of climate change. If they did, the population might increase instead concludes a new international study with participation from the Centre for Macroecology, Evolution and Climate at the University of Copenhagen. The study highlights the importance of integrating climate models in management plans for biodiversity.
"Our ...
Paper-thin e-skin responds to touch by lighting up
2013-07-22
BERKELEY — A new milestone by engineers at the University of California, Berkeley, can help robots become more touchy-feely, literally.
A research team led by Ali Javey, UC Berkeley associate professor of electrical engineering and computer sciences, has created the first user-interactive sensor network on flexible plastic. The new electronic skin, or e-skin, responds to touch by instantly lighting up. The more intense the pressure, the brighter the light it emits.
"We are not just making devices; we are building systems," said Javey, who also has an appointment as ...
A first in front line immunity research
2013-07-22
Monash University researchers have gained new insight into the early stages of our immune response, providing novel pathways to develop treatments for diseases from multiple sclerosis to cancer.
In a study published today in Nature Immunology, a team of researchers led by Professor Paul Hertzog, of the Monash Institute of Medical Research (MIMR) and Professor Jamie Rossjohn, of the School of Biomedical Sciences, have characterised for the first time how interferon beta (IFNβ) proteins bind to cells and activate an immune response.
Produced when viral and bacterial ...
Mirror, mirror on the wall, who has the lowest noise of them all
2013-07-22
Although it may not be immediately obvious, the mechanical properties of optical components have a significant impact on the performance of lasers employed in precision sensing applications. Currently, the mechanical damping of such components, and the inherent mechanical fluctuations they generate, present a roadblock to further advancement of ever more precise measurements of time and space. For the past decade, researchers in the precision measurement community have been searching for a solution that allows for the development of high-reflectivity mirrors with simultaneously ...
Antioxidants -- too much of a good thing?
2013-07-22
In older men, a natural antioxidant compound found in red grapes and other plants -- called resveratrol -- blocks many of the cardiovascular benefits of exercise, according to research published today [22 July 2013] in The Journal of Physiology.
Resveratrol has received widespread attention as a possible anti-aging compound and is now widely available as a dietary supplement; much has been made of its role in explaining the cardiovascular health benefits of red wine, and other foods. But now, new research at The University of Copenhagen surprisingly suggests that eating ...
MS research could help repair damage affecting nerves
2013-07-22
Multiple sclerosis treatments that repair damage to the brain could be developed thanks to new research.
A study has shed light on how cells are able to regenerate protective sheaths around nerve fibres in the brain.
These sheaths, made up of a substance called myelin, are critical for the quick transmission of nerve signals, enabling vision, sensation and movement, but break down in patients with multiple sclerosis (MS).
The study, by the Universities of Edinburgh and Cambridge, found that immune cells, known as macrophages, help trigger the regeneration of myelin.
Researchers ...
Loss of African woodland may impact on climate, study shows
2013-07-22
Deforestation in parts of Africa could be reversed with changes to land use, a study suggests.
A more strategic approach to managing trees across the continent could have a positive impact on the changing climate, researchers say.
A pioneering study of African savannas by the University of Edinburgh has revealed deforestation in south-central Africa, driven by rising populations in the aftermath of war, and increasing demand for trees for agriculture and fuel.
This loss of forests threatens the ecosystem and the livelihood of populations. Scientists suggest that ...
Hydrogen cars quickened by Copenhagen chemists
2013-07-22
Climate friendly fuel cells for hydrogen cars have come one step closer. Researchers at the Department of Chemistry, University of Copenhagen, have shown how to build fuel cells that produce as much electricity as current models, but require markedly less of the rare and valuable precious metal platinum. Their discovery was published in the highly reputable periodical Nature Materials.
Cheaper hydrogen cars with new fuel cell design
Fuel cells ought to replace internal combustion engines in our cars. They are better for the climate and for the environment. Partly because ...
Failure to destroy toxic protein -- not buildup of protein itself -- contributes to Huntington's disease
2013-07-22
SAN FRANCISCO, CA—July 21, 2013—Alzheimer's, Huntington's, Parkinson's. Names forever linked to what they represent: diseases that ravage the brain's neurons and leave entire regions to wither and die. These and other so-called neurodegenerative diseases are often associated with the buildup of toxic proteins that lead to the death of neurons. But now, scientists at the Gladstone Institutes have discovered that the progression of disease is not due to the buildup of toxins itself, but rather in the individual neurons' ability to flush these toxins out. Further, they have ...