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The persistent activation of AT2 cells may contribute not only to emphysema but also to increased cancer susceptibility, given the well-established role of AT2 cells as potential cells-of-origin for lung adenocarcinoma ( This integrative model combining in vivo injury, 3D organoid culture, and transcriptomic profiling provides a powerful platform to dissect impaired regeneration in COPD and may inform precision-targeted regenerative therapies aimed at restoring lung homeostasis