RT Journal Article
SR Electronic
T1 Single-cell RNA-sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 753806
DO 10.1101/753806
A1 Arun C. Habermann
A1 Austin J. Gutierrez
A1 Linh T. Bui
A1 Stephanie L. Yahn
A1 Nichelle I. Winters
A1 Carla L. Calvi
A1 Lance Peter
A1 Mei-I Chung
A1 Chase J. Taylor
A1 Christopher Jetter
A1 Latha Raju
A1 Jamie Roberson
A1 Guixiao Ding
A1 Lori Wood
A1 Jennifer MS Sucre
A1 Bradley W. Richmond
A1 Ana P. Serezani
A1 Wyatt J. McDonnell
A1 Simon B. Mallal
A1 Matthew J. Bacchetta
A1 James E. Loyd
A1 Ciara M. Shaver
A1 Lorraine B. Ware
A1 Ross Bremner
A1 Rajat Walia
A1 Timothy S. Blackwell
A1 Nicholas E. Banovich
A1 Jonathan A. Kropski
YR 2019
UL http://biorxiv.org/content/early/2019/09/06/753806.abstract
AB Pulmonary fibrosis is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix. In order to comprehensively define the cell types, mechanisms and mediators driving fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing of single-cell suspensions from 10 non-fibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell types. We report a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF, and identify several previously unrecognized epithelial cell phenotypes including a KRT5−/KRT17+, pathologic ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially-discrete manner. Together these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease, and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis.One Sentence Summary Single-cell RNA-sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung.