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Single-Cell Deconvolution of Fibroblast Heterogeneity in Mouse Pulmonary Fibrosis.

Xie T et al.

Cell Reports. 2018 03 27; 22(13):3625-3640

https://doi.org/10.1016/j.celrep.2018.03.010PMID: 29590628

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.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Xie T ¹,
Wang Y ²,
Deng N ³,
Huang G ⁴,
Taghavifar F ⁴,
Geng Y ⁴,
Liu N ⁴,
Kulur V ⁴,
Yao C ⁴,
Chen P ⁴,
Liu Z ³,
Stripp B ⁴,
Tang J ²,
Liang J ⁴,
Noble PW ⁵,
Jiang D ⁶

Affiliations

¹ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ting.xie@cshs.org
² Genomics Core, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
³ Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
⁴ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
⁵ 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.noble@cshs.org
⁶ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. dianhua.jiang@cshs.org

This work was supported by:

NHLBI NIH HHS, United States
GrantID: T32 HL134637

NHLBI NIH HHS, United States
GrantID: P01 HL108793

NHLBI NIH HHS, United States
GrantID: R01 HL122068

NIAID NIH HHS, United States
GrantID: R01 AI052201

NHLBI NIH HHS, United States
GrantID: R01 HL060539

Classifications

Interesting Hypothesis
New Finding

Evaluations

Exceptional

20 Jun 2018

Giulio Gabbiani

+ -1 Evaluators

Although fibroblast phenotypic heterogeneity has been sporadically proposed for several years, this paper presents the first systematic tentative analysis of fibroblast heterogeneity in normal and pathologic tissues. Using single-cell RNA sequencing, the authors characterized six mesenchymal phenotypes in normal and seven mesenchymal phenotypes in fibrotic mouse lungs. This approach opens up the possibility of defining different fibroblastic phenotypes and possibly of following the evolution of these phenotypes during normal and pathological situations.