Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis

• DOI: 10.1172/jci.insight.90558
• Publication Date: 2016-12-07T16:00:58Z
• Authors: Yan Xu; Takako Mizuno; Anusha Sridharan; Yina Du; Minzhe Guo; Jie Tang; Kathryn A. Wikenh...; Anne-Karina T. Perl; Vincent A. Funari; Jason J. Gokey; Barry R. Stripp; Jeffrey A. Whitsett
• Keywords: Cell type; Pathogenesis; Alveolar cells

Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis normal human cells defined gene expression patterns with highly differentiated type 2 (AT2) cells, indicated enrichment RNAs critical for surfactant homeostasis. In contrast, scRNA-seq IPF identified 3 distinct subsets characteristics conducting basal goblet an additional atypical transitional that contributes pathological Individual frequently coexpressed 1 (AT1), AT2, selective markers, demonstrating "indeterminate" states differentiation not seen development. Pathway predicted aberrant activation canonical signaling via TGF-β, HIPPO/YAP, P53, WNT, AKT/PI3K. Immunofluorescence confocal microscopy disruption structure loss proximal-peripheral cells. analyses identities unique contributions The present study provides rich data source further explore health disease.