Researchers from the Perelman School of Medicine have discovered a new type of cell, the airway secretory cell in the lungs, that may help repair damage caused by diseases such as chronic obstructive pulmonary disease.
The study was published in Nature, a weekly international newspaper, and found that by comparing the genomes of human and mouse lungs, humans had a unique type of lung cells called airway secretory cells. These cells are one of many cell types that help maintain essential structures in the lungs. Researchers have noticed that disrupting RAS cells impairs lung functions in the same way that COPD affects the lungs, offering a possible treatment route.
COPD is a progressive lung disease that is characterized by chronic inflammation of the lungs and leads to damage to the alveoli – lung structures that exchange oxygen and carbon dioxide between the air and the bloodstream – over time. according to the Mayo Clinic. It is often caused by long-term exposure to cigarette smoke or other irritating gases or fumes. COPD affects about 10% of people in parts of the United States and caused more than 3 million deaths worldwide in 2019.
Differences between mouse lung cells — which are commonly used in research — and humans have meant that the mechanisms of COPD are relatively poorly understood, according to Penn Medicine. The RAS cells found reside near the alveoli and produce or secrete proteins that line the airways.
“The approach that we took was sort of a new evolutionary transcriptomic approach called single-cell transcriptomics, and what it allows you to do is take individual cells and analyze the transcriptomic signature of each cell type. Then you can use complex algorithms to separate cells that look alike and cells that are different from each other,” Maria Basil, author of the paper, told The Daily Pennsylvanian.
As Basil and the other researchers began to study individual cell populations, “it became very clear that there were populations that we hadn’t seen before,” leading to the discovery of the cell RAS. The researchers used organoid modeling to further investigate how RAS cells work.
In COPD, type 2 alveolar cells, which help regenerate the outer surfaces of the alveoli, are known to become abnormal. As the researchers cultured the organoids, they realized that RAS cells, in addition to their secretory function, could transform AT2 cells and regenerate its population.
The researchers found evidence that in people with COPD, defective AT2 cells may have acquired their abnormalities when converted from RAS cells, suggesting that cigarette smoke and similar irritants may disrupt RAS conversion in AT2.
Researchers hope that this newly discovered RAS-to-AT2 pathway can deepen understanding of the mechanisms of COPD and potentially lead to new ways to treat COPD that can improve lung function, expanding current treatments, such as anti- inflammation and oxygen therapy.
“This article skims the surface and identifies a few signaling pathways that appear to regulate [RAS cells]. I hope I will begin to understand better how [RAS] cells respond to insult will give us insight into the kinds of things we might try to target to improve lung function in patients with chronic lung disease,” Basil said.