Single-Cell Transcriptomic Analysis of Human Lung Provides Insights into the Pathobiology of Pulmonary Fibrosis
By P. Reyfman, J. Walter, N. Joshi, K. R. Anekalla, Alexandra McQuattie-Pimentel, Stephen Chiu, Ramiro Fernandez, Mahzad Akbarpour, Ching‐I Chen, Z. Ren and 39 more. American Journal of Respiratory and Critical Care Medicine, 2019
1,010 citations recorded by the source corpus.
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.
Subfields: Immunology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/0d978bd5d29f85b23d07d6645b47a3426bc3bbc5
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses (2020, methodology): “Totally, we curated single cell gene expression matrices of 13 human tissues, including lung [8] , liver [9] , ileum [10] , rectum [10] , blood [11] , bone marrow [12] , skin [13] , spleen [14] , esophagus [14] , colon [15] , eye [16] , stomach [17] and kidney [18] (Table S1) .”
- The protein expression profile of ACE2 in human tissues (2020, methodology): “…GSE130148 (Viera Braga, 2019), GSE134355 (Han et al., 2020) (samples: GSM4008628, GSM4008629, GSM4008630, GSM4008631, GSM4008632 and GSM4008633) and GSE122960 (Reyfman et al., 2019) (samples: GSM3489182, GSM3489185, GSM3489187, GSM3489189, GSM3489191, GSM3489193, GSM3489195 and GSM3489197).”
- Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis (2019, methodology): “Together, our results provide substantial insight into the complexity, heterogeneity, and plasticity of the peripheral lung in human disease, building upon molecular atlasing efforts in the diseased (21, 23, 24) and healthy lung (48).”
- Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov (2020, methodology): “Previous work has built up the online database for scRNA-Seq analysis of 8 normal human lung transplant donors 10 .”
- Pathogenesis of COVID-19 from a cell biologic perspective (2020, background): “However, this concept might need some revision, since single cell RNA indicates low level of ACE2 expression in conducting airway cells and no obvious cell type preference [5].”
- Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline (2022, background): “Validate serum biomarkers to identify those at risk of PPF (168, 169), which may be facilitated by proteomic analyses of peripheral blood and BAL fluid (169–171) and transcriptomic studies (170, 172, 173).”