Characterization of the COPD alveolar niche using single-cell RNA sequencing

Maor Sauler (), John E. McDonough (), Taylor S. Adams, Neeharika Kothapalli, Thomas Barnthaler, Rhiannon B. Werder, Jonas C. Schupp, Jessica Nouws, Matthew J. Robertson, Cristian Coarfa, Tao Yang, Maurizio Chioccioli, Norihito Omote, Carlos Cosme, Sergio Poli, Ehab A. Ayaub, Sarah G. Chu, Klaus H. Jensen, Jose L. Gomez, Clemente J. Britto, Micha Sam B. Raredon, Laura E. Niklason, Andrew A. Wilson, Pascal N. Timshel, Naftali Kaminski and Ivan O. Rosas
Additional contact information
Maor Sauler: Yale School of Medicine
John E. McDonough: Yale School of Medicine
Taylor S. Adams: Yale School of Medicine
Neeharika Kothapalli: Yale School of Medicine
Thomas Barnthaler: Yale School of Medicine
Rhiannon B. Werder: Center for Regenerative Medicine of Boston University and Boston Medical Center
Jonas C. Schupp: Yale School of Medicine
Jessica Nouws: Yale School of Medicine
Matthew J. Robertson: Baylor College of Medicine
Cristian Coarfa: Baylor College of Medicine
Tao Yang: Yale School of Medicine
Maurizio Chioccioli: Yale School of Medicine
Norihito Omote: Yale School of Medicine
Carlos Cosme: Yale School of Medicine
Sergio Poli: Mount Sinai Medical Center
Ehab A. Ayaub: Brigham and Women’s Hospital, Harvard Medical School
Sarah G. Chu: Brigham and Women’s Hospital, Harvard Medical School
Klaus H. Jensen: Intomics A/S
Jose L. Gomez: Yale School of Medicine
Clemente J. Britto: Yale School of Medicine
Micha Sam B. Raredon: Yale University
Laura E. Niklason: Yale University
Andrew A. Wilson: Center for Regenerative Medicine of Boston University and Boston Medical Center
Pascal N. Timshel: Intomics A/S
Naftali Kaminski: Yale School of Medicine
Ivan O. Rosas: Baylor College of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, however our understanding of cell specific mechanisms underlying COPD pathobiology remains incomplete. Here, we analyze single-cell RNA sequencing profiles of explanted lung tissue from subjects with advanced COPD or control lungs, and we validate findings using single-cell RNA sequencing of lungs from mice exposed to 10 months of cigarette smoke, RNA sequencing of isolated human alveolar epithelial cells, functional in vitro models, and in situ hybridization and immunostaining of human lung tissue samples. We identify a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance in COPD. Using transcriptomic network analyses, we predict capillary endothelial cells are inflamed in COPD, particularly through increased CXCL-motif chemokine signaling. Finally, we detect a high-metallothionein expressing macrophage subpopulation enriched in advanced COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD.

Date: 2022
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Citations: View citations in EconPapers (4)

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DOI: 10.1038/s41467-022-28062-9

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