Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis
| Autor: | Nichelle I. Winters, Jennifer M.S. Sucre, Carla L. Calvi, Linh T. Bui, Ana P. Serezani, Ross M. Bremner, Simon B. Mallal, Rajat Walia, Matthew J. Bacchetta, Lorraine B. Ware, Chase J. Taylor, Jamie Roberson, Wyatt J. McDonnell, Ciara M. Shaver, Bradley W. Richmond, Austin J. Gutierrez, Lance M. Peter, James E. Loyd, Christopher S. Jetter, Timothy S. Blackwell, Jonathan A. Kropski, Nicholas E. Banovich, Stephanie L. Yahn, Latha Raju, Lori Wood, Guixiao Ding, Arun C. Habermann, Mei-I Chung |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell type
Pulmonary Fibrosis Cell Population Diseases and Disorders Biology Extracellular matrix 03 medical and health sciences 0302 clinical medicine Pulmonary fibrosis medicine Humans education Fibroblast Lung Research Articles 030304 developmental biology 0303 health sciences education.field_of_study Multidisciplinary Sequence Analysis RNA Mesenchymal stem cell SciAdv r-articles respiratory system medicine.disease Fibrosis 3. Good health Cell biology Extracellular Matrix medicine.anatomical_structure 030228 respiratory system Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Single-cell RNA sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung. Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5−/KRT17+ pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis. |
| Databáze: | OpenAIRE |
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