Categorization of lung mesenchymal cells in development and fibrosis
Xue Liu,
Simon C. Rowan,
Jiurong Liang,
Changfu Yao,
Guanling Huang,
Nan Deng,
Ting Xie,
Di Wu,
Yizhou Wang,
Ankita Burman,
Tanyalak Parimon,
Zea Borok,
Peter Chen,
William C. Parks,
Cory M. Hogaboam,
S. Samuel Weigt,
John Belperio,
Barry R. Stripp,
Paul W. Noble,
Dianhua Jiang
Affiliations
Xue Liu
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Simon C. Rowan
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; UCD School of Medicine, Conway Institute, University College Dublin, Belfield, Ireland
Jiurong Liang
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Changfu Yao
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Guanling Huang
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Nan Deng
Genomics Core, Cedars-Sinai Medical Center, CA 90048, USA
Ting Xie
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Di Wu
Genomics Core, Cedars-Sinai Medical Center, CA 90048, USA
Yizhou Wang
Genomics Core, Cedars-Sinai Medical Center, CA 90048, USA
Ankita Burman
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Tanyalak Parimon
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Zea Borok
Division of Pulmonary and Critical Care Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA
Peter Chen
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
William C. Parks
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Cory M. Hogaboam
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
S. Samuel Weigt
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
John Belperio
Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
Barry R. Stripp
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Paul W. Noble
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Dianhua Jiang
Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Corresponding author
Summary: Pulmonary mesenchymal cells are critical players in both the mouse and human during lung development and disease states. They are increasingly recognized as highly heterogeneous, but there is no consensus on subpopulations or discriminative markers for each subtype. We completed scRNA-seq analysis of mesenchymal cells from the embryonic, postnatal, adult and aged fibrotic lungs of mice and humans. We consistently identified and delineated the transcriptome of lipofibroblasts, myofibroblasts, smooth muscle cells, pericytes, mesothelial cells, and a novel population characterized by Ebf1 expression. Subtype selective transcription factors and putative divergence of the clusters during development were described. Comparative analysis revealed orthologous subpopulations with conserved transcriptomic signatures in murine and human lung mesenchymal cells. All mesenchymal subpopulations contributed to matrix gene expression in fibrosis. This analysis would enhance our understanding of mesenchymal cell heterogeneity in lung development, homeostasis and fibrotic disease conditions.
