Gene Activity Analysis of IPF Lung Cells Pinpoints Abnormalities, Opens Way to Targeted Treatments

Wide access to potential molecular drug targets to treat pulmonary fibrosis is now possible, as researchers have mapped the complete set of genes active in individual lung cells from patients with idiopathic lung fibrosis and from healthy people.

The analysis, called single-cell RNA sequencing, also made it possible to single out several abnormal molecular pathways in the cells.

The study, “Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis,” published in the Journal of Clinical Investigation Insights, is likely to open up focused research on the molecular processes thought to contribute to the scarring of lung tissue.

Many studies have attempted to identify such drug targets. But using older methods, researchers were only able to detect changes in samples of whole tissue.

Now, researchers at Cincinnati Children’s Hospital Medical Center and Cedars-Sinai Medical Center in Los Angeles analyzed gene activity profiles from individual epithelial cells — the cell type lining the inside of the lungs. The cells were acquired either by brushing the airways or from tissue biopsies.

This approach allowed them to pinpoint the existence of different types of epithelial cells in healthy and diseased lungs. In healthy lungs, they found plenty of cells known as alveolar type 2 cells, which make sure that the inside surface of the lungs is moist. These cells are critical, both to normal breathing and to keeping microbes at bay.

Epithelial cells from idiopathic pulmonary fibrosis (IPF) patients could be divided into three types. While two were cell types also seen in healthy people, the third was nothing similar to what is found in normal lungs. In contrast to healthy cells, which usually have a specialized function, the abnormal cells had characteristics of several cell types — a feature shared with tumor cells. These cells are the ones driving disease processes.

The team identified abnormal activation of several well-known molecular signaling cascades in the diseased cells, and microscopic analysis confirmed that the cells had lost the normal appearance seen in lung alveoli.

“This paper identifies a number of novel targets and molecular pathways for IPF, for which there are pharmaceutical approaches,” Jeffrey Whitsett, MD, lead investigator and co-director of the Perinatal Institute at Cincinnati Children’s, said in a news release.