scholarly journals Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis

JCI Insight ◽  
2016 ◽  
Vol 1 (20) ◽  
Author(s):  
Yan Xu ◽  
Takako Mizuno ◽  
Anusha Sridharan ◽  
Yina Du ◽  
Minzhe Guo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Single Cell ◽  
Rna Sequencing ◽  
Single Cell Rna Sequencing

scholarly journals Single cell RNA Sequencing Identifies G-protein Coupled Receptor 87 as a Novel Basal Cell Marker of Distal Honeycomb Cysts in Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Katharina Heinzelmann ◽  
Qianjiang Hu ◽  
Yan Hu ◽  
Evgenia Dobrinskikh ◽  
Henrik M. Ulke ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Single Cell ◽  
Rna Sequencing ◽  
G Protein ◽  
Potential Contribution ◽  
G Protein Coupled Receptor ◽  
Basal Progenitor ◽  
Single Cell Rna Sequencing ◽  
G Protein Coupled

AbstractIdiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options. Epithelial reprogramming and honeycomb cysts are key pathological features of IPF, however, the IPF distal bronchiole cell subtypes and their potential contribution to IPF development and progression still remain poorly characterized. Here, we utilized single-cell RNA sequencing on enriched EpCAM+ cells of the distal IPF and Donor lung. Using the 10x Genomics platform, we generated a dataset of 47,881 cells and found distinct cell clusters, including rare cell types, such as suprabasal cells recently reported in the healthy lung. We identified G-protein coupled receptor (GPR) 87 as a novel surface marker of distal Keratin (KRT)5+ basal cells. GPR87 expression was localized to distal bronchioles and honeycomb cysts in IPF in situ by RNA Scope and immunolabeling. Modulation of GPR87 in primary human bronchial epithelial cells cultures resulted in impaired airway differentiation and ciliogenesis. Thus, GPR87 is a novel marker and potentially druggable target of KRT5+ basal progenitor cells likely contributing to bronchiole remodeling and honeycomb cyst development in IPF.

scholarly journals A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages

2019 ◽  
Vol 55 (1) ◽  
pp. 1900646 ◽  
Author(s):  
Nikita Joshi ◽  
Satoshi Watanabe ◽  
Rohan Verma ◽  
Renea P. Jablonski ◽  
Ching-I Chen ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Single Cell ◽  
Rna Sequencing ◽  
Single Molecule ◽  
Alveolar Macrophages ◽  
Lineage Tracing ◽  
Single Cell Rna Sequencing ◽  
Pharmacological Blockade ◽  
Macrophage Colony ◽  
Druggable Targets

Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms.We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescence in situ hybridisation to a spatially restricted model of asbestos-induced pulmonary fibrosis.We demonstrate that tissue-resident alveolar macrophages, tissue-resident peribronchial and perivascular interstitial macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche. Deletion of monocyte-derived alveolar macrophages but not tissue-resident alveolar macrophages ameliorated asbestos-induced lung fibrosis. Monocyte-derived alveolar macrophages were specifically localised to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including platelet-derived growth factor subunit A. Using single-cell RNA sequencing and spatial transcriptomics in both humans and mice, we identified macrophage colony-stimulating factor receptor (M-CSFR) signalling as one of the novel druggable targets controlling self-maintenance and persistence of these pathogenic monocyte-derived alveolar macrophages. Pharmacological blockade of M-CSFR signalling led to the disappearance of monocyte-derived alveolar macrophages and ameliorated fibrosis.Our findings suggest that inhibition of M-CSFR signalling during fibrosis disrupts an essential fibrotic niche that includes monocyte-derived alveolar macrophages and fibroblasts during asbestos-induced fibrosis.

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