Researchers at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California, San Francisco have unraveled a complex signaling process that reveals how different types of cells interact to create a heart.
It has long been known that heart muscle cells (cardiomyocytes) actively divide and expand in the embryo, but after birth this proliferative capacity is permanently lost. How this transition occurs has not been known.
In the current issue of the journal Developmental Cell, the scientists show that the secret to this switch lies in the cells that surround the muscle cells, known as fibroblasts, which send signals that tell cardiomyocytes to divide or get bigger in size. Manipulation of these signals may be able to induce cardiomyocytes to divide again for regenerative purposes after heart attacks.
Cells exist in a three-dimensional matrix with other cells. Reciprocal signaling between the neighboring cells, along with internally generated factors and signals, insure that the tissues attain the correct shape, size, and function. In heart development, prior to birth (embryogenesis) heart cells (cardiomyocytes) proliferate and develop into different parts of the heart. After birth, the cells no longer proliferate. Although they continue to grow, the inability to proliferate renders the heart unable to regenerate cells after they have been damaged as occurs in heart attacks. It has been suggested that cardiac fibroblasts, which are cells that surround the muscle cells and make up over half of the heart cells, might be important in embryogenesis, but little is known about their development and roles in the embryonic heart.
"We've always suspected that different cell types are involved in determining how a heart is built," said GICD Director and senior author Deepak Srivastava, MD. "Our research showed that the signals from cardiac fibroblasts contribute to the different responses of cardiomyocytes."
To replicate the cell interactions in the developing heart, the scientists developed a novel method of growing two distinct cell types together. By observing the cells in this system, they found that the embryonic cardiac fibroblasts promoted cell division by the cardiomyocytes more efficiently than adult cardiac fibroblasts. Furthermore, they found that fibronectin, collagen and a heparin-binding EGF-like growth factor are secreted specifically by the embryonic cardiac fibroblasts as signals to promote this cell division. These molecules act through another signaling molecule called b1 integrin, found on the surface of cardiomyocytes. The team confirmed their observations in mutant mice that lacked b1 integrin. The mutant mice had fewer myocardial cells and disruptions of the muscle integrity that eventually led to prenatal death.
"We found a major difference in the function of embryonic and adult cardiac fibroblasts. Embryonic cardiac fibroblasts promote myocyte proliferation, while adult fibroblasts promote myocyte hypertrophy," said Masaki Ieda, MD, PhD, Gladstone postdoctoral fellow and lead author on the study. "We are now trying to make adult cardiac fibroblasts more like their embryonic counterparts to induce cardiomyocyte proliferation in the adult."
"Fibroblasts are also abundant and integrally involved in many other tissues, including skin, breast, lung and some cancers. Our results may be relevant to the broader understanding of tissue development, function, and disease," said Dr. Srivastava.
Valerie Tucker | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology