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Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis

View ORCID ProfileTaylor S. Adams, View ORCID ProfileJonas C. Schupp, Sergio Poli, View ORCID ProfileEhab A. Ayaub, Nir Neumark, Farida Ahangari, View ORCID ProfileSarah G. Chu, Benjamin A. Raby, Giuseppe DeIuliis, Michael Januszyk, Qiaonan Duan, Heather A. Arnett, Asim Siddiqui, George R. Washko, View ORCID ProfileRobert Homer, Xiting Yan, View ORCID ProfileIvan O. Rosas, View ORCID ProfileNaftali Kaminski
doi: https://doi.org/10.1101/759902
Taylor S. Adams
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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  • ORCID record for Taylor S. Adams
Jonas C. Schupp
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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Sergio Poli
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Ehab A. Ayaub
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Nir Neumark
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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Farida Ahangari
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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Sarah G. Chu
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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  • ORCID record for Sarah G. Chu
Benjamin A. Raby
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
3Division of Pulmonary Medicine, Boston’s Children Hospital, Harvard Medical School, Boston, MA, USA
4Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Giuseppe DeIuliis
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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Michael Januszyk
5NuMedii, Inc., San Mateo, CA, USA
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Qiaonan Duan
5NuMedii, Inc., San Mateo, CA, USA
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Heather A. Arnett
5NuMedii, Inc., San Mateo, CA, USA
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Asim Siddiqui
5NuMedii, Inc., San Mateo, CA, USA
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George R. Washko
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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Robert Homer
6Department of Pathology, Yale School of Medicine, New Haven, CT, USA
7Pathology and Laboratory Medicine Service and VA CT HealthCare System, West Haven, CT, USA
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Xiting Yan
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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Ivan O. Rosas
2Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
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  • For correspondence: naftali.kaminski@yale.edu
Naftali Kaminski
1Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, United States
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  • ORCID record for Naftali Kaminski
  • For correspondence: naftali.kaminski@yale.edu
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Abstract

We provide a single cell atlas of Idiopathic Pulmonary Fibrosis (IPF), a fatal interstitial lung disease, focusing on resident lung cell populations. By profiling 312,928 cells from 32 IPF, 29 healthy control and 18 chronic obstructive pulmonary disease (COPD) lungs, we demonstrate that IPF is characterized by changes in discrete subpopulations of cells in the three major parenchymal compartments: the epithelium, endothelium and stroma. Among epithelial cells, we identify a novel population of IPF enriched aberrant basaloid cells that co-express basal epithelial markers, mesenchymal markers, senescence markers, developmental transcription factors and are located at the edge of myofibroblast foci in the IPF lung. Among vascular endothelial cells in the in IPF lung parenchyma we identify an expanded cell population transcriptomically identical to vascular endothelial cells normally restricted to the bronchial circulation. We confirm the presence of both populations by immunohistochemistry and independent datasets. Among stromal cells we identify fibroblasts and myofibroblasts in both control and IPF lungs and leverage manifold-based algorithms diffusion maps and diffusion pseudotime to infer the origins of the activated IPF myofibroblast. Our work provides a comprehensive catalogue of the aberrant cellular transcriptional programs in IPF, demonstrates a new framework for analyzing complex disease with scRNAseq, and provides the largest lung disease single-cell atlas to date.

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Posted September 09, 2019.
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Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis
Taylor S. Adams, Jonas C. Schupp, Sergio Poli, Ehab A. Ayaub, Nir Neumark, Farida Ahangari, Sarah G. Chu, Benjamin A. Raby, Giuseppe DeIuliis, Michael Januszyk, Qiaonan Duan, Heather A. Arnett, Asim Siddiqui, George R. Washko, Robert Homer, Xiting Yan, Ivan O. Rosas, Naftali Kaminski
bioRxiv 759902; doi: https://doi.org/10.1101/759902
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Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis
Taylor S. Adams, Jonas C. Schupp, Sergio Poli, Ehab A. Ayaub, Nir Neumark, Farida Ahangari, Sarah G. Chu, Benjamin A. Raby, Giuseppe DeIuliis, Michael Januszyk, Qiaonan Duan, Heather A. Arnett, Asim Siddiqui, George R. Washko, Robert Homer, Xiting Yan, Ivan O. Rosas, Naftali Kaminski
bioRxiv 759902; doi: https://doi.org/10.1101/759902

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