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Fig. 4 Lack of telomerase leads to low proliferation and increased apoptosis, inflammation, and melanocyte differentiation (A) Principal-component analysis (PCA) based on untargeted transcriptomics data of tumors from 9-month-old fish. (B) Gene set enrichment analysis (GSEA) hallmarks of late-stage melanoma of tert?/? fish compared to tert+/+ highlighting inflammatory pathways, senescence, and melanocyte differentiation. (C?E) Representative immunofluorescence images and respective quantifications of tert+/+ and tert?/? tumors. Scale bars: 20 ?m. (C) DNA damage by ?H2AX, (D) proliferation by PCNA, and (E) apoptosis by cleaved caspase-3 immunofluorescence of 9-month-old fish tumors (n ? 4; unpaired t test). Error bars represent ± SEM; each dot represents an individual tumor; n ? 4; ?p ? 0.05, ??p ? 0.01, and ????p ? 0.0001.