Fig. 5: Type V and Type D cells have features of distinct SCLC subtypes. | Nature Communications

Fig. 5: Type V and Type D cells have features of distinct SCLC subtypes.

From: p53 restoration in small cell lung cancer identifies a latent cyclophilin-dependent necrosis mechanism

Fig. 5

a Principal component analysis of Type D (4711-1, 4711-18, 4716-11) and Type V (4711-11, 4716-10, 4716-14) cell lines 72 h after treatment with vehicle (Control) or 4-OHT (Restored). b Volcano plots of RNA-sequencing data in untreated Type D and Type V cells. Colored dots represent genes that are differentially enriched (log2 fold-change greater-than 1 and false discovery rate (FDR)-adjusted P-value less-than 0.05) in Type D (n = 109 genes, red) or Type V (n = 57 genes, blue) cells. c Bubble plot representation of all GSEA hallmark gene sets with an FDR-adjusted P-value lower than 0.25 in untreated Type D (red) or Type V cells (blue). Normalized enrichment score (NES) plotted and the “SIZE” of each dot represents the number of genes within the gene set. d, e Dot plots indicating normalized enrichment scores of ‘Type D’ (d) and ‘Type V’ (e) gene signatures in human SCLC-ASCL1 (n = 47) and SCLC-NEUROD1 (n = 15) cell lines. Single sample GSEA analysis was performed to quantify enrichment of specific gene signatures in gene expression datasets from human SCLC cell lines obtained using CellMiner-SCLC (Tlemsani et al. 2020). Error bars represent mean ± s.d. Statistical significance was determined by two-tailed Student’s t-test. Highlighted cell lines were used in downstream analysis. f–j Flow cytometry-assisted cell viability assay in human SCLC (H2081, H2915, H69, HCC2433, HCC4004) cell lines infected with either Ad:GFP, Ad:p53-GFP, CsA and/or Nutlin for 48–72 h. Each symbol represents a technical replicate (n = 3). Error bars represent mean ± s.d. k–o Immunoblot analysis of p53 and GFP in human SCLC cell lines used in (f–j). Vinculin is loading control. Source data are provided as a Source Data file.

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