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

doi:10.1016/j.isci.2021.102551

Categorization of lung mesenchymal cells in development and fibrosis

iScience. 2021 May 19;24(6):102551. doi: 10.1016/j.isci.2021.102551. eCollection 2021 Jun 25.

Authors

Xue Liu¹, Simon C Rowan^{1

2}, Jiurong Liang¹, Changfu Yao¹, Guanling Huang¹, Nan Deng³, Ting Xie¹, Di Wu³, Yizhou Wang³, Ankita Burman¹, Tanyalak Parimon¹, Zea Borok⁴, Peter Chen¹, William C Parks¹, Cory M Hogaboam¹, S Samuel Weigt⁵, John Belperio⁵, Barry R Stripp¹, Paul W Noble¹, Dianhua Jiang^{1

6}

Affiliations

¹ Department of Medicine and Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
² UCD School of Medicine, Conway Institute, University College Dublin, Belfield, Ireland.
³ Genomics Core, Cedars-Sinai Medical Center, CA 90048, USA.
⁴ Division of Pulmonary and Critical Care Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA 90033, USA.
⁵ Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Abstract

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.

Keywords: cell biology; organizational aspects of cell biology; pathophysiology.

Abstract

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