Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis
| Autor: | Monique Hinchcliff, Monica Chi, Manu Jain, Anna P. Lam, Vince K. Morgan, Gökhan M. Mutlu, Ali Shilatifard, Luís A. Nunes Amaral, A. Christine Argento, Satoshi Watanabe, Robert D. Guzy, SeungHye Han, Ankit Bharat, Colin T. Gillespie, Stacy A. Marshall, Kishore R. Anekalla, Ching I. Chen, Kiwon Nam, Alexandra C. McQuattie-Pimentel, Alexander V. Misharin, Remzi Bag, Annette S. Flozak, Harris Perlman, Karen M. Ridge, Rohan Verma, Benjamin D. Singer, James M. Walter, Jane Dematte, Catherine A. Bonham, Stephen Chiu, Ramiro Fernandez, Ziyou Ren, Cara L. Hrusch, Saul Soberanes, Anjana Yeldandi, Francisco J. Gonzalez-Gonzalez, Nikita Joshi, Hiam Abdala-Valencia, Trevor T. Nicholson, G. R. Scott Budinger, Sangeeta Bhorade, Anne I. Sperling, Paul A. Reyfman, Mahzad Akbarpour, Jacob I. Sznajder, Deborah R. Winter, Robert B. Hamanaka, Kinola J.N. Williams, Cara J. Gottardi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Cell type Pathology medicine.medical_specialty Population Cell Critical Care and Intensive Care Medicine Transcriptome 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine Fibrosis Pulmonary fibrosis medicine Animals Humans 030212 general & internal medicine education Cells Cultured education.field_of_study Sequence Analysis RNA business.industry Stem Cells Editorials Epithelial Cells medicine.disease Idiopathic Pulmonary Fibrosis 3. Good health Disease Models Animal medicine.anatomical_structure 030228 respiratory system Female Stem cell business |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.201712-2410oc |
| Popis: | 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: | OpenAIRE |
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