Single-cell RNA sequencing of lung cells from bleomycin-induced and doxycycline-inducible TGF-ß transgenic mouse models of pulmonary fibrosis

This study aimed to elucidate how epithelial–macrophage interactions contribute to pulmonary fibrosis. Using bleomycin-induced and genetic mouse models (Mif-2 KO, SPC-Cul3 KO, SPC-Mif KO, CX3CR1-Cd74 KO, PF4-Cd74 KO, and TGF-ß transgenic mice), we performed single-cell transcriptomic profiling of lung cells and compared them with wild-type controls. Overall design: Single-cell RNA sequencing was performed on lung cells from wild-type and genetically modified mice, including Mif-2 KO, SPC-Cul3 KO, SPC-Mif KO, CX3CR1-Cd74 KO, PF4-Cd74 KO, and doxycycline-inducible TGF-ß transgenic mice. Pulmonary fibrosis was induced by intratracheal bleomycin, with lung tissues collected at day 10 and 14 or by two weeks of doxycycline administration to activate TGF-ß transgene expression. Gene expression profiles were compared across models and wild-type controls to identify cell type–specific changes associated with fibrosis progression.