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Single-Cell Expression Analysis of Nasal Polyps Suggests Mechanisms of Chronic Inflammation

NEW YORK (GenomeWeb) – In an effort to elucidate molecular mechanisms of chronic inflammatory diseases, researchers at Brigham and Women's Hospital, the Massachusetts Institute of Technology, and the Broad Institute have profiled the transcriptomes of human nasal polyps and nasal scrapings by single-cell RNA sequencing.

In a paper published in Nature today, they reported a number of differences between epithelial cells of the two sample types, in particular a reduction in cellular diversity in the nasal polyps that resulted from functional shifts in their basal cells. In particular, they demonstrated that basal cells retain a memory of being exposed to cytokines IL-4 and IL-13.

"We propose that basal cells form 'memories' of chronic exposure to an inflammatory [type two immunity] environment, shifting the entire cellular ecosystem away from productive differentiation and propagating disease," they wrote. "Future work will seek to determine the relative contributions of memory stored in distinct cellular compartments to develop the most effective mechanisms by which to erase them."

Nasal polyps result from chronic allergic inflammation and often recur after surgery. According to co-corresponding author Nora Barrett of Brigham and Women's Hospital, the goal of her research is "to understand why the inflammatory process persists once it begins and to uncover the cause of these conditions."

For their study, the researchers performed single-cell RNA sequencing on more than 18,000 cells from 12 surgically removed nasal polyps spanning the disease spectrum. They use Seq-Well, a single-cell sequencing approach developed by MIT researchers and published last year. They then compared the results to data from more than 18,000 single cells from nine nasal scrapings, which represented healthy tissue.

Overall, they found that the diversity of epithelial cell types was reduced in the nasal polyps, which contained few glandular and ciliated cells and were enriched in basal cells. The latter appeared to be stuck in their ability to differentiate into other cell types. This reduction in cellular diversity might be explained by differences in gene expression the researchers found between polyp and non-polyp basal progenitor cells.

In addition, they revealed that a transcriptional program that is activated by cytokines IL-4 and IL-13 is strongly induced in basal progenitor cells from polyps, suggesting a possible treatment with an antibody that blocks the shared IL-4/IL-13 receptor subunit.

According to the statement, the research team "hopes to use the new information to develop a genetic signature that would allow clinicians to take a swab of nasal mucosa to test for lung conditions."