Dataset Information

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

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.

SUBMITTER: Rao W

PROVIDER: S-EPMC7294989 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

Rao Wei W Wang Shan S Duleba Marcin M Niroula Suchan S Goller Kristina K Xie Jingzhong J Mahalingam Rajasekaran R Neupane Rahul R Liew Audrey-Ann AA Vincent Matthew M Okuda Kenichi K O'Neal Wanda K WK Boucher Richard C RC Dickey Burton F BF Wechsler Michael E ME Ibrahim Omar O Engelhardt John F JF Mertens Tinne C J TCJ Wang Wei W Jyothula Soma S K SSK Crum Christopher P CP Karmouty-Quintana Harry H Parekh Kalpaj R KR Metersky Mark L ML McKeon Frank D FD Xian Wa W

Cell 20200415 4

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 dominat ...[more]

PMID: 32298651

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Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with no known cure, characterized by the formation of scar tissue in the lungs, leading to respiratory failure. Although the exact cause of IPF remains unclear, the condition is thought to result from a combination of genetic and environmental factors. One of the most widely used animal models to study IPF is the bleomycin-induced lung injury model in mice. In this model, the administration of the chemotherapeutic agent bleomycin causes pulmonary inflammation and fibrosis, which closely mimics the pathological features of human IPF. Numerous recent investigations have explored the functions of various categories of stem cells in the healing process of lung injury induced by bleomycin in mice, documenting the beneficial effects and challenges of this approach. Differentiation of stem cells into various cell types and their ability to modulate tissue microenvironment is an emerging aspect of the regenerative therapies. This review article aims to provide a comprehensive overview of the role of stem cells in repairing bleomycin-induced lung injury. It delves into the mechanisms through which various types of stem cells, including mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, and lung resident stem cells, exert their therapeutic effects in this specific model. We have also discussed the unique set of intermediate markers and signaling factors that can influence the proliferation and differentiation of alveolar epithelial cells both during lung repair and homeostasis. Finally, we highlight the challenges and opportunities associated with translating stem cell therapy to the clinic for IPF patients. The novelty and implications of this review extend beyond the understanding of the potential of stem cells in treating IPF to the broader field of regenerative medicine. We believe that the review paves the way for further advancements in stem cell therapies, offering hope for patients suffering from this debilitating and currently incurable disease.

Dataset Information

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

Publications

Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

Similar Datasets

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