New Basal Cell Marker as target in Idiopathic Pulmonary Fibrosis
G-protein coupled receptor marks bronchiole remodeling by distal Keratin 5+ basal progenitor cells
Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options. Epithelial reprogramming and honeycomb cysts are key pathological features of IPF. However, the IPF distal bronchiole cell subtypes and their potential contribution to IPF development and progression still remain poorly characterized.
Researchers around Group Leader Mareike Lehmann from LHI/CPC-M (Lehmann Lab) in collaboration with researchers from the University of Pittsburgh now discovered a new basal cell marker that is strongly connected to the formation of honeycomb cysts in IPF.
The researchers utilized single-cell RNA sequencing on enriched EpCAM+ cells of the distal IPF and Donor lung. Using the 10x Genomics platform, they generated a dataset of 47,881 cells and found distinct cell clusters, including rare cell types, such as suprabasal cells recently reported in the healthy lung.
The Lehmann Lab identified G-protein coupled receptor (GPR) 87 as a novel surface marker of distal Keratin (KRT)5+ basal cells. GPR87 expression was localized to distal bronchioles and honeycomb cysts in IPF in situ by RNA Scope and immunolabeling. Modulation of GPR87 in primary human bronchial epithelial cells cultures resulted in impaired airway differentiation and ciliogenesis.
Thus, GPR87 is a novel marker and potentially druggable target of KRT5+ basal progenitor cells likely contributing to bronchiole remodeling and honeycomb cyst development in IPF.
The Lehmann Lab (LHI/CPC-M) aims to understand how aging predisposes the lung to the development of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). In particular, the lab investigates how these diseases can be replicated as far as possible without animal experiments. Learn more here.