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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174390/ https://www.ncbi.nlm.nih.gov/pubmed/32317643 http://dx.doi.org/10.1038/s41467-020-15647-5 |
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author | 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 |
author_facet | 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 |
author_sort | Tsukui, Tatsuya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7174390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71743902020-04-28 Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis 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 Nat Commun Article 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. Nature Publishing Group UK 2020-04-21 /pmc/articles/PMC7174390/ /pubmed/32317643 http://dx.doi.org/10.1038/s41467-020-15647-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title | Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title_full | Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title_fullStr | Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title_full_unstemmed | Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title_short | Collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
title_sort | collagen-producing lung cell atlas identifies multiple subsets with distinct localization and relevance to fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174390/ https://www.ncbi.nlm.nih.gov/pubmed/32317643 http://dx.doi.org/10.1038/s41467-020-15647-5 |
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