Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis

Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations wit...

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Veröffentlicht in:	Nature communications Jg. 11; H. 1; S. 1920 - 16
Hauptverfasser:	Tsukui, Tatsuya, Sun, Kai-Hui, Wetter, Joseph B., Wilson-Kanamori, John R., Hazelwood, Lisa A., Henderson, Neil C., Adams, Taylor S., Schupp, Jonas C., Poli, Sergio D., Rosas, Ivan O., Kaminski, Naftali, Matthay, Michael A., Wolters, Paul J., Sheppard, Dean
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 21.04.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	13/1 13/31 13/51 14/19 14/35 38/32 38/39 38/88 38/90 38/91 631/1647/514/2254 64/110 64/60 692/699/1785 Adoptive transfer Animals Architecture Cell Separation Collagen Collagen - chemistry Extracellular Matrix Proteins - metabolism Female Fibroblasts Fibroblasts - metabolism Fibrosis Flow Cytometry Gene sequencing Green Fluorescent Proteins - metabolism Heterogeneity High-Throughput Nucleotide Sequencing Homeostasis Humanities and Social Sciences Humans Hybridization Idiopathic Pulmonary Fibrosis - pathology Localization Lung - metabolism Lung - pathology Lung diseases Lungs Male Mice Mice, Inbred C57BL multidisciplinary Phenotype Phenotypes Pulmonary fibrosis Pulmonary Fibrosis - metabolism Pulmonary Fibrosis - pathology Respiration Disorders - metabolism Ribonucleic acid RNA Scars Science Science (multidisciplinary) Scleroderma Single-Cell Analysis Subpopulations
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Zusammenfassung:	Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1 -expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1 -expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis. Collagen production by lung cells is critical to maintain organ architecture but can also drive pathological scarring. Here the authors perform single cell RNA sequencing of collagen-producing lung cells identifying a subset of pathologic fibroblasts characterized by Cthrc1 expression which are concentrated within fibroblastic foci in fibrotic lungs and show a pro-fibrotic phenotype.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-15647-5