{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:42:01Z","timestamp":1791232921361,"version":"4.1.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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<jats:sub>2<\/jats:sub>)-exposed mouse lungs. By day 56, SiO<jats:sub>2<\/jats:sub> induced significant epithelial proliferation, followed with a distinct C0 subset emerging as the dominant population. C0 cells co-expressed surfactant genes (<jats:italic>Sftpc<\/jats:italic>, <jats:italic>Scgb3a2<\/jats:italic>), mesenchymal markers (<jats:italic>Vim<\/jats:italic>, <jats:italic>Mmp12<\/jats:italic>), and pro-inflammatory cytokines (<jats:italic>Ccl6<\/jats:italic>, <jats:italic>S100a8\/a9<\/jats:italic>), 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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1609616","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T01:22:18Z","timestamp":1749172938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Single-cell and spatial transcriptomics reveal a stress-induced EMT-like epithelial subset driving immune activation in silica-injured 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