Figure 1.

Tet2 KO inhibits squamous transition in KL model. (A) Heatmap of DNA methylation factors and adeno/squamous lineage markers in normal lung, ADC, and SCC of the KL mouse model. (B) Western blot analysis for TET2, p63, KRT5, and TTF1 in KL-ADC and KL-SCC tumors. β-Actin served as the internal loading control. Parallel blots using the same samples. (C) Schematic illustration of the KL and KLT mouse model. W, week. (D and E) (D) Representative 5hmC IHC staining of KL and KLT tumors. Scale bar: 50 μm. Statistical analysis is also shown (E). 30 representative images for each group were counted. (F) Representative H&E staining for whole lungs of KL and KLT models. The whole lungs are reused in Fig. S2 E. * indicates SCC. Scale bar: 1 mm. H&E staining with high magnification is shown. Scale bar: 50 μm. (G) Representative IHC staining for TTF1, p63, SOX2, and KRT5 in KL and KLT mice. Scale bar: 50 μm. (H–J) Statistical analyses of the AST incidence (H), the number (I), and burden (J) of SCC in KL (n = 10) and KLT (n = 10) mice. (K) Kaplan–Meier survival curves of KL (n = 6) and KLT (n = 5) mice. (L) Representative Ki-67 IHC staining and statistical analyses in KL and KLT tumors. Scale bar: 50 μm. 30 representative images for each group were counted. Data in B, D, and E represent one experiment of three independent repeats, and F–L represents one experiment of two independent repeats. **P < 0.01, ****P < 0.0001 by two-tailed unpaired Student’s t test (E, I, J, and L), Fisher’s exact test (H), log-rank (Mantel–Cox) test (K). Data are represented as mean ± SD. Source data are available for this figure: SourceData F1.

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