Chronic rhinosinusitis is distinct from your average case of seasonal allergies. It causes the sinuses to become inflamed and swollen for months to years at a time, leading to difficulty breathing and other symptoms that make patients feel miserable. In some people, this condition also produces tissue outgrowths known as nasal polyps, which, when severe enough, have to be removed surgically.

By performing a genome-wide analysis of thousands of single cells from human patients, MIT and Brigham and Women’s Hospital researchers have created the first global cellular map of a human barrier tissue during inflammation. Analysis of these data led them to propose a novel mechanism that may explain what sustains chronic rhinosinusitis.

Their findings also offer an explanation for why some rhinosinusitis patients develop nasal polyps, which arise from epithelial cells that line the respiratory tract. Furthermore, their study may have broader implications for how researchers think about and treat other chronic inflammatory diseases of barrier tissues, such as asthma, eczema, and inflammatory bowel disease.

“We saw major gene-expression differences in subsets of epithelial cells which had been previously obscured in bulk tissue analyses,” says Alex K. Shalek, the Pfizer-Laubach Career Development Assistant Professor of Chemistry, a core member of MIT’s Institute for Medical Engineering and Science (IMES), and an extramural member of the Koch Institute for Integrative Cancer Research, as well as an associate member of the Ragon and Broad Institutes.

“When you look across the entire transcriptome, comparing cells from patients with different disease statuses over thousands of genes, you can start to understand the relationships between them and discover which transcriptional programs have supplanted the usual ones,” Shalek says.

The lead authors of the paper, which appears in the August 22 issue of Nature, are Jose Ordovas-Montanes, an IMES postdoc fellow supported by the Damon Runyon Cancer Research Foundation, and Daniel Dwyer, a research fellow at Brigham and Women’s Hospital. Shalek and Nora Barrett, an assistant professor of medicine at Brigham and Women’s, are the paper’s senior authors.