Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.
Adult
Aged
Animals
Female
Fibrosis
/ physiopathology
Humans
Inflammation
/ pathology
Lung
/ metabolism
Male
Metaplasia
/ physiopathology
Mice
Middle Aged
Neutrophils
/ immunology
Pneumonia
/ pathology
Pulmonary Disease, Chronic Obstructive
/ genetics
Single-Cell Analysis
/ methods
Stem Cells
/ metabolism
COPD
chronic lung disease
fibrosis
inflammation
lung
metaplasia
myofibroblasts
neutrophils
p63
single cell cloning
stem cells
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
14 05 2020
14 05 2020
Historique:
received:
26
07
2019
revised:
26
11
2019
accepted:
20
03
2020
pubmed:
17
4
2020
medline:
5
1
2021
entrez:
17
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32298651
pii: S0092-8674(20)30340-8
doi: 10.1016/j.cell.2020.03.047
pmc: PMC7294989
mid: NIHMS1580700
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
848-864.e18Subventions
Organisme : NCI NIH HHS
ID : U24 CA228550
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK054759
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK047967
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL129795
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL108808
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA241600
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136961
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK115445
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES005605
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136370
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138510
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests W.X., F.D.M., W.R., S.W., J.X., M.D., and M.V. have filed patents related to technologies used in the present work. M.V., F.D.M., and W.X. have financial interests in Nüwa Medical Systems, Houston, TX, USA and Tract pharmaceuticals, Houston, TX, USA. Nuwa Medical Systems is a trade name of Tract Pharmaceuticals.
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