PT  - JOURNAL ARTICLE
AU  - Katharina Heinzelmann
AU  - Qianjiang Hu
AU  - Yan Hu
AU  - Evgenia Dobrinskikh
AU  - Henrik M. Ulke
AU  - Meshal Ansari
AU  - Colton Leavitt
AU  - Carol Mirita
AU  - Tammy Trudeau
AU  - Maxwell L. Saal
AU  - Pamela Rice
AU  - Bifeng Gao
AU  - William J. Janssen
AU  - Ivana V. Yang
AU  - Herbert B. Schiller
AU  - Eszter K. Vladar
AU  - Mareike Lehmann
AU  - Melanie Königshoff
TI  - Single cell RNA Sequencing Identifies G-protein Coupled Receptor 87 as a Novel Basal Cell Marker of Distal Honeycomb Cysts in Idiopathic Pulmonary Fibrosis
AID  - 10.1101/2021.09.03.458324
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.03.458324
4099  - http://biorxiv.org/content/early/2021/09/03/2021.09.03.458324.short
4100  - http://biorxiv.org/content/early/2021/09/03/2021.09.03.458324.full
AB  - 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. Here, we utilized single-cell RNA sequencing on enriched EpCAM+ cells of the distal IPF and Donor lung. Using the 10x Genomics platform, we 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. We 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.Competing Interest StatementThe authors have declared no competing interest.