Single-Cell RNA Sequencing Detects 3 Subsets of Aberrant Epithelial Cells Involved in Idiopathic Pulmonary Fibrosis
Published Dec. 8, 2016
JCI Insight
Thanks to the power of single-cell RNA sequencing, a research team led by scientists at Cincinnati Children’s may have cracked open the genetic secrets of the lethal lung disease, idiopathic pulmonary fibrosis (IPF).
IPF inflames, scars and reconfigures lung tissues in ways that can destroy alveoli, causing life-threatening loss of lung function. Despite years of studying whole tissue samples, scientists have been unable to identify the genetic, cellular and molecular processes that fuel the disease.
A study led by Yan Xu, PhD, and Jeffrey Whitsett, MD, co-director of the Perinatal Institute, working in collaboration with investigators at Cedars-Sinai Medical Center in Los Angeles, took a new approach.
The team conducted what they believe to be the first single-cell RNA sequence analysis of normal and diseased human lung tissues. This produced a detailed genetic blueprint of the epithelial cell types involved in IPF progression.
Analysis of normal lung epithelial cells found gene patterns linked to fully formed alveolar type 2 lung cells. Analysis of IPF cells identified three subsets of cell types that reflect disruptions of cell differentiation within the microenvironment of IPF.
Some cells shared characteristics of conducting airway and alveolar epithelial cells. Some reflected a mix of airway basal and goblet cells. Others appeared to be an atypical type of transitional cell. None of these cell types had been identified in studies of normal lung development.
Now, their gene expression characteristics provide new opportunities for further investigation. “This paper identifies a number of novel targets and molecular pathways for IPF, for which there are pharmaceutical approaches,” Whitsett says.
Eventually, this line of research could identify marker genes that would make it possible to diagnose lung diseases, or monitor treatment, by collecting and analyzing airway cells obtained through biopsy or bronchial brushing.
