Extended Data Fig. 11. KACs are enriched in lungs and they precede the formation of Kras^G12D tumours in an AT2 lineage reporter tobacco carcinogenesis mouse model.

a, Representative IF analysis of KRT8, GFP, and LAMP3 in GFP-labelled AT2-derived mouse lung organoids (n = 3 wells per condition) derived from tamoxifen-exposed AT2 reporter mice at EOE to saline (n = 4 mice) or NNK (n = 5 mice). Scale bar: 10 μm. b, UMAP distribution of GFP⁺ cells at 3 months following NNK exposure or saline and coloured by alveolar or tumour subsets. c, Proportions and average expression levels of select marker genes for mouse normal alveolar cell lineages and tumour cells defined in b. d, Fraction of Kras^G12D cells across alveolar and early tumour subsets. Absolute numbers of Kras^G12D cells are indicated on top of each bar. e, UMAPs of GFP⁺ cells from tumour-bearing AT2 reporter mice at 3 months following NNK or saline and coloured by presence of Kras^G12D mutation or expression of KAC, AT1, and AT2 signatures. f, UMAPs showing distribution of alveolar and tumour cell subsets (left) as well as cells with Kras^G12D mutation (right) by treatment (saline or NNK). g, Trajectories of GFP⁺ cells from tumour-bearing reporter mice at 3 months following NNK or saline coloured by inferred pseudotime (left), differentiation (middle), and cell lineage and showing subset composition (right). h, CytoTRACE (left) and pseudotime (right) scores across GFP⁺ subsets. Box-and-whisker definitions are similar to Extended Data Fig. 1f. n cells in each box-and-whisker: AT2 = 144; Early–AT2-like tumour = 144; KAC–KAC-like = 288; AT1 = 72.