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!
Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg
New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences