Tissue Type(s): Lung

Contributed by: Alexander V Misharin Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois and Paul A Reyfman, Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine.

Manuscript: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells (https://www.biorxiv.org/content/10.1101/2020.04.19.049254v1)

Description: This study allows one to visualize and query genes as well as explore cell types, technical batches, and cell metrics associated with the manuscript. If published, this version of the data set is focused on the manuscript and is a subset of what may be made available by the original manuscript.

Original Reyfman, Paul A., et al. "Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis." American journal of respiratory and critical care medicine 199.12 (2019): 1517-1536.

Full dataset: The full dataset availability is described in the publication, and relevant processed data is shared here in the downloads tab. In addition, data is shared here https://www.nupulmonary.org/resources/.

Abstract:

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.