Molecular analysis identifies differences between healthy lung and lungs of people with cystic fibrosis

Healthy airways (left) show well-defined layers of ciliated cells (green) and basal stem cells (red). In airways affected by cystic fibrosis (right), the layers are disrupted, and scientists identified a transitioning cell type that combines properties of both stem cells and ciliated cells (red and green in the same cell).
Credit: Nature Medicine

Researchers have developed a molecular catalog of cells in healthy lungs and the lungs of people with cystic fibrosis.

The catalog, described in the journal Nature Medicine, reveals new subtypes of cells and illustrates how the disease changes the cellular makeup of the airways. For the study, researchers compared tissue samples taken from lungs removed from 19 people with cystic fibrosis, all of whom had received lung transplants. Researchers used healthy lung tissue donated by 19 people who died from other causes.

Researchers used single-cell RNA sequencing, a technology that allowed them to analyze thousands of cells at the same time and classify them into subtypes based on their gene expression patterns. Using a novel computer-based bioinformatics approach, they then compared the gene expression patterns of the various cells and created a catalog of cell types and subtypes present in healthy airways and those affected by cystic fibrosis. This included some previously unknown subtypes and highlighting how the disease alters the cellular landscape of the airways.

The findings, researchers say, could help them in their search for specific cell types that represent prime targets for genetic and cell therapies for cystic fibrosis. The study was partly funded by NHLBI.

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