Air pollution causes stemness and progenitor dysfunction in AECII: the potential for COPD development.

<bold>Background:</bold> Air pollution is recognized as a risk factor for chronic obstructive pulmonary disease (COPD); however, the underlying mechanisms are still limited. This study aims to investigate the effects of air pollution on stemness and progenitor functions in type II alveolar epithelial cells (AECII) of COPD. <bold>Methods:</bold> B6. Sftpc-CreERT2 mice were intratracheally instilled 8.5 mg/kg diesel exhaust particles (DEP) for 24 hrs to develop acute pulmonary inflammation. Single-cell RNA sequence (scRNAseq) analysis was conducted in the lungs to identify the stemness and progenitor gene expression in SFTPC+ LAMP3+ AECII. Also, COPD Fischer 344 rats were established by 3-month exposure to ambient unconcentrated traffic-related air pollution using a whole-body exposure system. Immunofluorescence staining was conducted to determine the stemness and progenitor protein expression in SFTPC+ cells of the acute inflammation and COPD rats. <bold>Results:</bold> We observed an upregulation of the genes Sox9, Mycn, Epcam, Sox2, Pou5f1, Nanog, Cldn4, Tcf7, Foxm1, and Wnt7b in SFTPC+ LAMP3+ cells in mice with DEP-induced acute inflammation, as indicated by scRNAseq analysis. Conversely, the genes Foxp2, Igf1, and Igf1r were found to be downregulated. In air pollution-induced COPD mice, there was a significant increase in the expression of OCT4. Additionally, SOX9 expression in AECII of COPD mice was increased. <bold>Conclusion:</bold> Our results suggest that air pollution regulates stemness and progenitor functions in AECII of COPD. These findings offer insights into the lung microenvironment's complexity and the regulation of AECII stem/progenitor cells, contributing to the understanding and potentially treating COPD.