Findings from animal study have implications for disorders such as chronic obstructive pulmonary disease
A new collaborative study describes a way that lung tissue can regenerate after injury. The team found that lung tissue has more dexterity in repairing tissue than once thought. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Duke University, including co-senior authors Jon Epstein, MD, chair of the department of Cell and Developmental Biology, and Brigid L.M Hogan, Duke Medicine, along with co-first authors Rajan Jain, MD, a cardiologist and instructor in the Department of Medicine and Christina E. Barkauskas, also from Duke, report their findings in Nature Communications
Adult lung cells regenerating: Type 1 cells are green. Type 2 cells are red. New Type 2 derived from Type 1 cells are yellow. Nuclei are blue
Jon Epstein, MD & Rajan Jain, MD, Perelman School of Medicine at the University of Pennsylvania, and Christina Barkauskas & Brigid Hogan, Duke University
"It's as if the lung cells can regenerate from one another as needed to repair missing tissue, suggesting that there is much more flexibility in the system than we have previously appreciated," says Epstein. "These aren't classic stem cells that we see regenerating the lung. They are mature lung cells that awaken in response to injury. We want to learn how the lung regenerates so that we can stimulate the process in situations where it is insufficient, such as in patients with COPD [chronic obstructive pulmonary disease]."
The two types of airway cells in the alveoli, the gas-exchanging part of the lung, have very different functions, but can morph into each other under the right circumstances, the investigators found. Long, thin Type 1 cells are where gases (oxygen and carbon dioxide) are exchanged - the actual breath. Type 2 cells secrete surfactant, a soapy substance that helps keep airways open. In fact, premature babies need to be treated with surfactant to help them breathe.
The team showed in mouse models that these two types of cells originate from a common precursor stem cell in the embryo. Next, the team used other mouse models in which part of the lung was removed and single cell culture to study the plasticity of cell types during lung regrowth. The team showed that Type 1 cells can give rise to Type 2 cells, and vice-versa.
The Duke team had previously established that Type 2 cells produce surfactant and function as progenitors in adult mice, demonstrating differentiation into gas-exchanging Type 1 cells. The ability of Type I cells to give rise to alternate lineages had not been previously reported.
"We decided to test that hypothesis about Type 1 cells," says Jain. "We found that Type 1 cells give rise to the Type 2 cells over about three weeks in various models of regeneration. We saw new cells growing back into these new areas of the lung. It's as if the lung knows it has to grow back and can call into action some Type 1 cells to help in that process."
This is one of the first studies to show that a specialized cell type that was thought to be at the end of its ability to differentiate can revert to an earlier state under the right conditions. In this case, it was not by using a special formula of transcription factors, but by inducing damage to tell the body to repair itself and that it needs new cells of a certain type to do that.
The team is also applying the approaches outlined in this paper to cells in the intestine and skin to study basic ideas of stem cell maintenance and differentiation to relate back to similar mechanisms in the heart. They also hope to apply this knowledge to such other lung conditions as acute respiratory distress syndrome and idiopathic pulmonary fibrosis, where the alveoli cannot get enough oxygen into the blood.
"We want to know if we can, and how, to make new lung cells as work-arounds for diseased alveoli cells," says Jain.
This work was supported in part by funds from the National Heart, Lung and Blood Institute (U01HL110942, RO1HL071546, K08HL119553-02, K08HL122521-01, UO1HL111018), as well as the NIH Lung Repair and Regeneration Consortium (UO1HL110967) and the Cotswold Foundation.
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 $4.9 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 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 $409 million awarded in the 2014 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; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.
Karen Kreeger | EurekAlert!
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering