Journal article
Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis
Cell, Vol.181(4), pp.848-864.e18
05/14/2020
DOI: 10.1016/j.cell.2020.03.047
PMCID: PMC7294989
PMID: 32298651
Abstract
Chronic obstructive pulmonary disease (COPD) is a progressive condition of chronic bronchitis, small airway obstruction, and emphysema that represents a leading cause of death worldwide. While inflammation, fibrosis, mucus hypersecretion, and metaplastic epithelial lesions are hallmarks of this disease, their origins and dependent relationships remain unclear. Here we apply single-cell cloning technologies to lung tissue of patients with and without COPD. Unlike control lungs, which were dominated by normal distal airway progenitor cells, COPD lungs were inundated by three variant progenitors epigenetically committed to distinct metaplastic lesions. When transplanted to immunodeficient mice, these variant clones induced pathology akin to the mucous and squamous metaplasia, neutrophilic inflammation, and fibrosis seen in COPD. Remarkably, similar variants pre-exist as minor constituents of control and fetal lung and conceivably act in normal processes of immune surveillance. However, these same variants likely catalyze the pathologic and progressive features of COPD when expanded to high numbers.
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•COPD lung is dominated by three pathogenic stem cell variants•These variants are epigenetically committed to metaplastic lesions found in COPD•Variants drive key COPD features of inflammation, fibrosis, and airway obstruction•Similar variants in fetal and normal lung likely serve sentinel functions
The hallmark features of COPD (inflammation, fibrosis, and mucus hypersecretion) are driven by distinct pathogenic progenitors which pre-exist as minor populations in healthy lungs but dominate in the disease state relative to normal lung stem cells.
Details
- Title: Subtitle
- Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis
- Creators
- Wei Rao - University of HoustonShan Wang - University of HoustonMarcin Duleba - University of HoustonSuchan Niroula - University of HoustonKristina Goller - University of HoustonJingzhong Xie - University of HoustonRajasekaran Mahalingam - University of HoustonRahul Neupane - University of HoustonAudrey-Ann Liew - University of HoustonMatthew Vincent - Nüwa Medical Systems, Houston, TX 77479, USAKenichi Okuda - University of North Carolina at Chapel HillWanda K. O’Neal - Marsico Lung Center, University of North Carolina, Chapel Hill, NC 27599, USARichard C. Boucher - University of North Carolina at Chapel HillBurton F. Dickey - The University of Texas MD Anderson Cancer CenterMichael E. Wechsler - National Jewish HealthOmar Ibrahim - University of ConnecticutJohn F. Engelhardt - University of IowaTinne C.J. Mertens - The University of Texas Health Science Center at HoustonWei Wang - The University of Texas Health Science Center at HoustonSoma S.K. Jyothula - Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USAChristopher P. Crum - Brigham and Women's HospitalHarry Karmouty-Quintana - The University of Texas Health Science Center at HoustonKalpaj R. Parekh - University of IowaMark L. Metersky - University of ConnecticutFrank D. McKeon - University of HoustonWa Xian - University of Houston
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.181(4), pp.848-864.e18
- DOI
- 10.1016/j.cell.2020.03.047
- PMID
- 32298651
- PMCID
- PMC7294989
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000005, name: U.S. Department of Defense; DOI: 10.13039/100000897, name: Cystic Fibrosis Foundation; DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100004917, name: Cancer Prevention and Research Institute of Texas
- Language
- English
- Date published
- 05/14/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Cardiothoracic Surgery; Internal Medicine
- Record Identifier
- 9984284340202771
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