Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis.

Autor:	Rao W; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Wang S; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Duleba M; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Niroula S; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Goller K; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Xie J; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Mahalingam R; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Neupane R; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Liew AA; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA., Vincent M; Nüwa Medical Systems, Houston, TX 77479, USA., Okuda K; Marsico Lung Center, University of North Carolina, Chapel Hill, NC 27599, USA., O'Neal WK; Marsico Lung Center, University of North Carolina, Chapel Hill, NC 27599, USA., Boucher RC; Marsico Lung Center, University of North Carolina, Chapel Hill, NC 27599, USA., Dickey BF; Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wechsler ME; Department of Medicine, National Jewish Health, Denver, CO 80206, USA., Ibrahim O; Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Connecticut School of Medicine, Farmington, CT 06032, USA., Engelhardt JF; Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA., Mertens TCJ; Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Wang W; Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Jyothula SSK; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Crum CP; Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02215, USA., Karmouty-Quintana H; Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA., Parekh KR; Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Surgery, Division of Cardiothoracic Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA., Metersky ML; Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Connecticut School of Medicine, Farmington, CT 06032, USA., McKeon FD; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA. Electronic address: fdmckeon@uh.edu., Xian W; Stem Cell Center, Department of Biology and Biochemistry, University of Houston, Houston, TX 77003, USA. Electronic address: wxian@uh.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2020 May 14; Vol. 181 (4), pp. 848-864.e18. Date of Electronic Publication: 2020 Apr 15.
DOI:	10.1016/j.cell.2020.03.047
Abstrakt:	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. Competing Interests: 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. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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