From this single "basal" cell, a small, squat stem cell that divides to replenish the lung lining layer, scientists created 3-D hollow spheres that were lined inside with both ciliary and secretory cells.
This 3-D model can be used to study dynamic processes underlying lung diseases, including cancer, said Brigid Hogan, Ph.D., chair of the Duke Department of Cell Biology and senior researcher of the study, which was published in PNAS Early Edition.
"Now that we have this 3-D model and information about the gene expression 'signature' of basal cells, we are in a strong position to see what happens when lung-cell behavior goes awry," Hogan said. "We might, for example, be able to activate an oncogene (a cancer-causing gene) or other factors to see how lung cancer might develop in the airways. Amazingly, almost nothing is known about lung basal cells, which are so important to health and make up nearly a third of the cells in the human airways."
Normally, basal stem cells maintain the airways by turning over slowly into new ciliated cells and secretory cells. Ciliated cells resemble waving brooms that sweep along particles and distribute secretions that are needed in the airways, and secretory cells provide the antibacterial and lubricating secretions. These two types of cells are neatly arranged in equal proportions in healthy lung airways. However, when lungs are affected by maladies like cancer, chemical damage, cystic fibrosis or asthma, the balance of these cells can be thrown off.
By learning the role these basal cells play in maintaining the airway tissue, the scientists were able to create an entirely new way to study them.
"We put a lot of effort into developing this model, so that we and other groups can test the ability of individual airway progenitor cells to divide and differentiate under defined conditions," said lead author Jason Rock, Ph.D., a postdoctoral associate in the Duke Department of Cell Biology. "Now we can change the culture conditions to investigate mechanisms that underlie pathological conditions, including chronic asthma and cancer."
The work was a collaboration of cell biologists, Mark Onaitis, M.D., of the Department of Surgery at Duke University Medical Center, and Scott H. Randell, PhD., of the Cystic Fibrosis/Pulmonary Research and Treatment Center at the University of North Carolina in Chapel Hill.
The scientists isolated basal cells, set each separately in a gel suspension, and observed the cells growing into a hollow sphere as they divided. Analysis shows that the basal cells remain on the outside of the sphere, while inside the hollow was lined in an equal arrangement of cilial and secretory cells, as in nature.
"This basal cell is making daughters, which are polarized and retain their orientation so that they will form a structure with luminal (airway lining) cells on the inside," Hogan said. "Only about 5 percent of the basal cells we isolated and put into gel formed these spheres; perhaps these are the ones that are normally ready to leap into action when they are challenged."
After painstakingly sorting individual green fluorescent mouse basal cells from the other lung tissue cells, the scientists studied the genes expressed in these mouse cells using microarray technology. They found more than 600 genes preferentially expressed in the basal cells compared with the other cells.
"We found that many of these genes are similar to genes expressed in stem cells in other tissues," Hogan said. "We think these genes are helping these cells to stay 'quiet' and keep them from dividing until they get the right signal."
The researchers also found that one gene expressed in the basal cells encodes a surface receptor, also found on human lung basal cells. "This meant we were able to use a labeled antibody against this receptor to efficiently extract human lung basal cells to create the human bronchospheres for study," Hogan said.
Other authors included Emma Rawlins, Yun Lu, Cheryl P. Clark, and Yan Xue of the Duke Department of Cell Biology. This research is supported by grants from the National Institutes of Health, a Howard Hughes Medical Institute Early Career Grant and a Parker B. Francis Fellowship.
Mary Jane Gore | EurekAlert!
NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University
How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine