A Novel MIP-1–Expressing Macrophage Subtype in BAL Fluid from Healthy Volunteers

Tissue availability remains an important limitation of single-cell genomic technologies for investigating cellular heterogeneity in human health and disease. BAL represents a minimally invasive approach to assessing an individual’s lung cellular environment for diagnosis and research. However, the lack of high-quality, healthy lung reference data is a significant obstacle to using single-cell approaches to study a plethora of lung diseases. Here, single-cell RNA sequencing was performed on over 40,000 cells isolated from the BAL of four healthy volunteers. The study assessed the variability of gene expression across macrophages and defined a distinct subpopulation of cells expressing a set of genes associated with Macrophage Inflammatory Protein 1 (MIP-1). RNA in situ hybridization and reanalysis of published lung single-cell data validated the presence of this macrophage subpopulation. Thus, the present study characterizes lung macrophage heterogeneity in healthy individuals and provides a valuable resource for future studies to understand the lung environment in health and disease.