Single cell RNA Sequencing Identifies G-protein Coupled Receptor 87 as a Basal Cell Marker Expressed in Distal Honeycomb Cysts in Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a devastating and life-threatening lung disease characterized by epithelial reprogramming and increased extracellular matrix deposition leading to loss of lung function. A prominent histopathological structure in the IPF lung are aberrant bronchioles filled with mucus, referred to as honeycomb cysts. These heterogeneous bronchiolized areas feature clusters of simple epithelium with Keratin (KRT)5+ basal-like cells interspersed with pseudostratified epithelium containing differentiated, hyperplastic epithelial cells as well as aberrant ciliated cells. Recent single-cell RNA sequencing studies of the lung epithelium shed further light into cellular subtypes unique to IPF, including basaloid KRT5-/KRT17+ cells present in the distal lung. However, IPF distal bronchiole cell subtypes still remain poorly characterized and their disease contribution remains underinvestigated. Using single-cell RNA sequencing of enriched EpCAM+ lung cells of the distal IPF lung, we identified G-protein coupled receptor (GPR) 87, as a marker of distal bronchioles and KRT5+ IPF basal cells contributing to impaired airway differentiation and honeycombing. Single-cell suspensions from three donor lungs and three lungs from patients with IPF were enriched into Epcam+ cells and went through single cell RNA-seq analysis. ***Raw data not available due to patient privacy concerns***