Decoding coal-induced pulmonary endothelial injury using single-cell omics.

Pulmonary endothelial injury is a critical factor in the pathogenesis and progression of coal pneumoconiosis. However, the precise mechanisms underlying this injury remain poorly understood. To address this, we established a coal pneumoconiosis mouse model by chronic intranasal coal dust exposure over 9 months. We applied single-cell RNA sequencing (scRNA-seq) to lung tissues from coal-exposed and control mice and resolved four endothelial subpopulations-arterial (ArtECs), lymphatic (LECs), venous (VenECs), and capillary (CapECs). Our findings reveal that coal dust exposure induces endothelial injury by increasing oxidative stress, suppressing proliferation, and compromising cell adhesion and junction integrity. We observed a significant reduction in endothelial cell numbers in the coal-exposed group, with CapECs and ArtECs more severely affected than VenECs and LECs. Oxidative phosphorylation pathways were upregulated, whereas adhesion pathways (e.g., focal adhesion, ECM-receptor interaction) were downregulated across EC (endothelial cell) subtypes; elevated ROS partially corroborated these transcriptomic patterns. Furthermore, CellChat analysis indicated disruption of key proliferative signaling between macrophages and ECs, including TGF-β and GDF axes. Additionally, macrophage-derived LAMP2 and LC3B signals may contribute to EC loss. Collectively, these findings demonstrate that coal dust exposure alters the composition and functionality of lung endothelial cells through a combination of intrinsic and extrinsic mechanisms, offering valuable insights into potential therapeutic strategies for pulmonary complications associated with coal pneumoconiosis.