Fig. 7: An LSD1 inhibitor reverses NE differentiation.
a Heatmap of median GI50 values for A549-shLuc and A549-shMEN1 cells treated with 96 small molecule inhibitor compounds for 3 days. The results were ranked according to the difference in sensitivity between A549-shLuc and A549-shMEN1 cells as determined by the GI50 ratios (GI50 A549-shLuc/A549-shMEN1). b Men1f/f and Men1Δ/Δ MEF cells were treated with SP2509 for 24 h, and the levels of H3K4me3, H3K4me2, H3K4me1, and H3K9me3 modifications in histone extracts were determined via western blotting. c Quantification of the SA-β-gal-positive IMR-90 cells shown in Supplementary Fig. 7b. Cells were transfected with siRNA for 48 h and then treated with 1 μm SP2509 for 4 h. SA-β-gal staining was performed 2 days after exposure to 5 Gy of IR. d Axial microCT images in the indicated planes from WT, KS, KMS, and SP2509-treated (25 mg/kg i.p. injection) KMS mice at 1, 2, and 4 weeks. e Quantification of lung and body weight for KMS-vehicle and SP2509-treated KMS mice at 51 days (WT con: n = 3; WT SP2509: n = 3; KMS con: n = 6; KMS SP2509: n = 6). f Brightfield images of lung tissue from KMS and SP2509-treated KMS mice at 51 days. g Representative images of SA-β-gal staining and IHC staining in consecutive lung sections from KMS-vehicle, and SP2509-treated KMS mice at 51 days. Scale bars, 60 μm. h H&E images (left) and IHC staining for the indicated proteins in lung sections from KMS-vehicle and SP2509-treated KMS mice at 51 days (n = 7 per group). Scale bars, 1 mm (H&E) and 20 μm (IHC). Data are represented as mean ± SD in c and as mean ± SEM in e. Dots in e depict individual samples. Significance determined by Two-tailed unpaired t tests in c and e are indicated. ****p < 0.0001. Results in b are representative of three independent experiments. Source Data are provided as a Source Data file.
