Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis.

Autor: Reyfman PA; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Walter JM; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Joshi N; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Anekalla KR; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., McQuattie-Pimentel AC; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Chiu S; 2 Division of Thoracic Surgery, Department of Surgery., Fernandez R; 2 Division of Thoracic Surgery, Department of Surgery., Akbarpour M; 2 Division of Thoracic Surgery, Department of Surgery., Chen CI; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Ren Z; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Verma R; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Abdala-Valencia H; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Nam K; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Chi M; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Han S; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Gonzalez-Gonzalez FJ; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Soberanes S; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Watanabe S; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Williams KJN; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Flozak AS; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Nicholson TT; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Morgan VK; 3 Division of Rheumatology, Department of Medicine., Winter DR; 3 Division of Rheumatology, Department of Medicine., Hinchcliff M; 3 Division of Rheumatology, Department of Medicine., Hrusch CL; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Guzy RD; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Bonham CA; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Sperling AI; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Bag R; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Hamanaka RB; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Mutlu GM; 4 Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois; and., Yeldandi AV; 5 Department of Pathology, and., Marshall SA; 6 Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Shilatifard A; 6 Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Amaral LAN; 7 Department of Chemical and Biological Engineering, Weinberg College of Arts and Sciences, Northwestern University, Evanston, Illinois., Perlman H; 3 Division of Rheumatology, Department of Medicine., Sznajder JI; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Argento AC; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine.; 2 Division of Thoracic Surgery, Department of Surgery., Gillespie CT; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine.; 2 Division of Thoracic Surgery, Department of Surgery., Dematte J; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Jain M; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Singer BD; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine.; 6 Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Ridge KM; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Lam AP; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Bharat A; 2 Division of Thoracic Surgery, Department of Surgery., Bhorade SM; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Gottardi CJ; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Budinger GRS; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine., Misharin AV; 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine.
Jazyk: angličtina
Zdroj: American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2019 Jun 15; Vol. 199 (12), pp. 1517-1536.
DOI: 10.1164/rccm.201712-2410OC
Abstrakt: Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Databáze: MEDLINE
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