Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis
Ting Xie,
Yizhou Wang,
Nan Deng,
Guanling Huang,
Forough Taghavifar,
Yan Geng,
Ningshan Liu,
Vrishika Kulur,
Changfu Yao,
Peter Chen,
Zhengqiu Liu,
Barry Stripp,
Jie Tang,
Jiurong Liang,
Paul W. Noble,
Dianhua Jiang
Affiliations
Ting Xie
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Yizhou Wang
Genomics Core, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Nan Deng
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Guanling Huang
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Forough Taghavifar
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Yan Geng
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Ningshan Liu
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Vrishika Kulur
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Changfu Yao
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Peter Chen
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Zhengqiu Liu
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Barry Stripp
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Jie Tang
Genomics Core, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Jiurong Liang
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Paul W. Noble
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Dianhua Jiang
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Summary: Fibroblast heterogeneity has long been recognized in mouse and human lungs, homeostasis, and disease states. However, there is no common consensus on fibroblast subtypes, lineages, biological properties, signaling, and plasticity, which severely hampers our understanding of the mechanisms of fibrosis. To comprehensively classify fibroblast populations in the lung using an unbiased approach, single-cell RNA sequencing was performed with mesenchymal preparations from either uninjured or bleomycin-treated mouse lungs. Single-cell transcriptome analyses classified and defined six mesenchymal cell types in normal lung and seven in fibrotic lung. Furthermore, delineation of their differentiation trajectory was achieved by a machine learning method. This collection of single-cell transcriptomes and the distinct classification of fibroblast subsets provide a new resource for understanding the fibroblast landscape and the roles of fibroblasts in fibrotic diseases. : Xie et al. have analyzed mesenchymal cell subpopulations at single-cell resolution and have demonstrated known subtypes and a newly emerging subtype during pulmonary fibrosis in mouse lung. Keywords: single-cell RNA-seq, fibroblast, lung mesenchymal cells, fibrosis
