Two nationally recognized experts in cloning and stem cell science from the University of Houston, Wa Xian and Frank McKeon, are reporting that five lung stem cell variants dominate the lungs of patients with advanced cystic fibrosis (CF), and that these variants drive key aspects of CF pathology including inflammation, fibrosis and mucin secretion.
Cystic fibrosis is an inherited and progressive disease that causes long-lasting lung infections and limits the ability to breathe. It is caused by a defect in a gene called the cystic fibrosis transmembrane conductance regulator (CFTR) and affects nearly 40,000 people in the United States. Defects in the CFTR gene lead to the production of abnormally sticky and thick mucus that clogs organs, particularly lungs, causing chronic lung disease marked by infections and inflammation.
Recently introduced drugs known as CFTR modulators act to rescue the function to the mutant CFTR gene and yield remarkable improvements in lung function of CF patients. However, in patients with established lung disease, lung inflammation remains despite treatment with CFTR modulators. This persistence is concerning as inflammation is thought to be a key factor in the progression of CF lung disease.
This gap in CFTR modulator efficacy renders the work of the Xian-McKeon laboratory particularly relevant.
Using single cell cloning technology that detailed stem cell heterogeneity in lungs from patients with COPD and idiopathic pulmonary fibrosis (IPF), we identified five stem cell variants common to lungs of patients with advanced CF, including three that show hyperinflammatory gene expression profiles