Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured lung

作者：Tao Wang, Jianfeng Hao, Bing Li, Ahjol Hyraht, Jialing Wang, Henglei Xia, Qingbin Wu, Wei Gao, Congxia Chen, Chuanqing Yu, Xiuqun Gong, Ting Li, Mei Zhang, Yinghai Xie, Xinrong Tao · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1609616 · 被引用次数：7 · 研究领域：Neonatal Respiratory Health Research、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Tracheal and airway disorders

The mechanism that lung epithelial cells regulate immune responses during chronic injury still remains unclear. Here, we combined single-cell RNA sequencing with spatial transcriptomics to track epithelial dynamics in silica (SiO 2 )-exposed mouse lungs. By day 56, SiO 2 induced significant epithelial proliferation, followed with a distinct C0 subset emerging as the dominant population. C0 cells co-expressed surfactant genes ( Sftpc , Scgb3a2 ), mesenchymal markers ( Vim , Mmp12 ), and pro-inflammatory cytokines ( Ccl6 , S100a8/a9 ), reflecting a hybrid phenotype. Spatial and cell-cell interaction analyses showed C0 cells engaging macrophages and neutrophils through SPP1-CD44, APP-CD74, and GRN-MARCO signaling, driving immune recruitment and activation. Pseudotime and CytoTRACE analyses indicated that C0 cells represent a late-stage, low-stemness state with epithelial-mesenchymal transition (EMT)-like features. Taken together, these findings reveal a novel, stress-induced epithelial subset that amplifies immune crosstalk and tissue remodeling, offering new perspectives on silica-induced lung injury.