ArticleNature genetics2026
Aberrant cellular communities underlying disease heterogeneity in chronic obstructive pulmonary disease.
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Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
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Who cites it
20 citing papers in PubMed.
- Preclinical models of COPD: a state of the art review.The European respiratory journal · 2026Review
- Integrated Bioinformatics and Experimental Validation to Identify Shared Sialylation-Related Signatures in Emphysematous and Fibrotic Lung Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Pyroptosis in chronic obstructive pulmonary disease: Beyond the canonical NLRP3/Caspase-1/GSDMD pathway.Immunologic research · 2026Review
- Cooperation, Defection, and Collapse: A Multiscale Game Theory Framework for Emphysema Progression.Cells · 2026Review
- Defective alveolar regeneration in emphysema: identifying dysfunctional cellular crosstalk and novel therapeutic opportunities for tissue repair.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- SPEAK: Spatial Prompting with Expert Aligned Knowledge for Tissue Domain Identification in Spatial Transcriptomics.bioRxiv : the preprint server for biology · 2026Article
- Spatial transcriptomics reveals compartment-specific cytotoxic T cell crosstalk with AT2 and goblet cells in advanced COPD.Biomarker research · 2026Article
- HHIP's dynamic role in epithelial wound healing reveals a potential mechanism of COPD susceptibility.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Investigating human lung resilience, its evolutionary history and its relation to COPD.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- AT2-intrinsic Z-AAT expression drives conserved inflammatory and proteotoxic stress responses and predisposes to emphysema.bioRxiv : the preprint server for biology · 2026Article
- Aberrant cellular communities underlying disease heterogeneity in chronic obstructive pulmonary disease.Nature genetics · 2026Article
- A Single Cell Atlas of the COPD Lung Identifies Inflammatory Reprogramming in Fibroblasts.International journal of chronic obstructive pulmonary disease · 2026Article
- Macrophage spatiotemporal plasticity in pulmonary diseases: decoding the niche at single-cell resolution.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction and the regulatory cell death crosstalk network in chronic obstructive pulmonary disease: from oxidative stress mechanisms to targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Integrative machine learning and single-cell analysis identifies nicotine-related diagnostic genes and myeloid remodeling in COPD.Frontiers in immunology · 2026Article
- Epitranscriptomics, immunometabolism, and NETosis: unlocking novel mechanisms of traditional Chinese medicine in COPD.Frontiers in immunology · 2026Review
- Oxidative stress-driven epigenetic reprogramming of immune cells in COPD: from epitranscriptomic and metabolic crosstalk to treatable traits.Frontiers in immunology · 2026Review
- Inhaled Targeted Nano-Drug Delivery Systems for COPD: Precision Solutions to Clinical Barriers.International journal of nanomedicine · 2026Review
Corrections and comments
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Authors and funding
32 authors.
Yuening Zhang *Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Huanhuan Wei *Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5741-4114
Jessica Nouws *Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-3347-3595
Wenhao JiangPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Reginald M BrewsterPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Jenny P NguyenPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-2952-6877
SiRu LiangPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0009-0003-7243-9119
Samuel M PassPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Weiwei WangDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Florine CollinDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
Angela Taravella OillDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-4408-7211
Sang-Hun KimPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Saul S SillerDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.
Jinjiang LiuDepartment of Applied Analytics, Columbia University, New York City, NY, USA.
Amy Y ZhaoPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Phillip HansbroCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, New South Wales, Australia.
Charles Dela CruzDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Clemente BrittoPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Jose GomezPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Suzanne M CloonanSchool of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0001-5301-9926
Erica L HerzogPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
TuKiet T LamDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
Nicholas E BanovichDivision of Bioinnovation and Genome Sciences, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.ORCID http://orcid.org/0000-0003-2604-3247
Micha Sam B RaredonDepartment of Anesthesiology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1441-6122
Xuchen ZhangDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Stefano MangiolaDepartment of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0001-7474-836X
Robert J HomerDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2055-5885
Naftali KaminskiPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-5917-4601
John McDonoughDepartment of Medicine, McMaster University, Firestone Institute for Respiratory Health, St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
Francesca PolverinoPulmonary Division, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Xiting YanPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Maor SaulerPulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA. maor.sauler@yale.edu.ORCID http://orcid.org/0000-0001-5240-7978
Funding
Yale/NIDA Neuroproteomics Research CenterP30DA018343 · NIDA · YALE UNIVERSITY · PI Kenneth Robert WILLIAMS · 2004 to 2026
$37.1MSpatiotemporal genomic regulation of disease initiation and progression in pulmonary fibrosisR01HL145372 · NHLBI · TRANSLATIONAL GENOMICS RESEARCH INST · PI Nicholas Eli Banovich, Jonathan Andrew Kropski · 2019 to 2026
$6.0MGenomic Analysis of Tissue and Cellular Heterogeneity in IPFR01HL127349 · NHLBI · YALE UNIVERSITY · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2015 to 2025
$5.9MUse of the Src Family Kinase Inhibitor Saracatinib in the Treatment of Pulmonary FibrosisUH3TR002445 · NCATS · NATIONAL JEWISH HEALTH · PI DOWNEY, GREGORY PAUL, KAMINSKI, NAFTALI · 2019 to 2021
$5.0MResearch Training in AnesthesiaT32GM086287 · NIGMS · YALE UNIVERSITY · PI ROBERT SCHONBERGER · 2009 to 2026
$3.7MSystems Biology of a MicroRNA Network in Neutrophilic AsthmaR01HL153604 · NHLBI · YALE UNIVERSITY · PI GOMEZ-VILLALOBOS, JOSE LUIS · 2020 to 2024
$3.4MB cell-adaptive Immune Profile in Emphysema-predominant COPDR01HL149744 · NHLBI · UNIVERSITY OF ARIZONA · PI POLVERINO, FRANCESCA · 2020 to 2024
$3.4MRole of MIF and CD74 in the pathogenesis of emphysemaR01HL155948 · NHLBI · YALE UNIVERSITY · PI BUCALA, RICHARD J, SAULER, MAOR · 2021 to 2025
$3.4MEpithelial Protective Effects of Thyroid Hormone Signaling in FibrosisR01HL141852 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$3.4MNormal Aging Lung Cell Atlas (NALCA)U01HL145567 · NHLBI · YALE UNIVERSITY · PI KAMINSKI, NAFTALI · 2019 to 2022
$2.8MGraph Learning of Cell-cell Communications in Spatial TranscriptomicsR01LM014087 · NLM · YALE UNIVERSITY · PI WANG, ZUOHENG, YAN, XITING · 2022 to 2025
$1.5M6500 QTrap Mass Spectrometer for Yale UniversityS10OD018034 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2014 to 2014
$514kNCATS NIH HHS UH3 TR002445NHLBI NIH HHS F30 HL162459NHLBI NIH HHS R01 HL127349NHLBI NIH HHS R01 HL141852NHLBI NIH HHS R01 HL145372NHLBI NIH HHS R01 HL149744NHLBI NIH HHS R01 HL153604NHLBI NIH HHS R01 HL155948NHLBI NIH HHS R21 HL161723NHLBI NIH HHS R21 HL173512NHLBI NIH HHS U01 HL145567NIDA NIH HHS P30 DA018343NIGMS NIH HHS T32 GM086287NIH HHS S10 OD018034NIH HHS S10 OD019967NLM NIH HHS R01 LM014087
Abstract
Chronic obstructive pulmonary disease (COPD) is clinically and molecularly heterogeneous. To investigate COPD heterogeneity, we profiled lung tissue by single-nucleus RNA sequencing from 141 study participants (1,516,727 nuclei) and identified shifts in cell composition and emergent cell states that correlated with lung function, emphysema and composite symptom scores. Epithelial regenerative states peaked in early COPD and declined thereafter, whereas inflamed nonimmune cells and profibrotic/remodeling states, together with select immune populations, expanded with disease progression. Clustering study participants by the proportion of pathologic cells coupled with spatial transcriptomics identified distinct patterns of cellular co-occurrence within spatially localized niches. Proteomic analyses identified plasma biomarkers of cell states and their impact on the extracellular matrix. Mediation and cell communication analyses revealed cell-autonomous and intercellular communication networks associated with disease. These data define the cellular landscape of COPD heterogeneity, revealing molecular drivers and biomarkers that could inform therapeutic strategies.
Indexed as
Pulmonary Disease, Chronic ObstructiveBiomarkersCell CommunicationDisease ProgressionHumansLungMaleProteomicsSpatial TranscriptomicsTranscriptomeBiomarkers
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