Epigenetic Disordering Drives Stemness, Senescence Escape and Tumor Heterogeneity bulk RNAseq

We show that overexpressing high levels of the epigenetic regulator and oncogene, human UHRF1, in zebrafish hepatocytes rapidly induced changes in the DNA methylome and disordering, DNA damage, cell cycle arrest, senescence, and acquisition of progenitor like features.

These changes are observed within 1 day of human UHRF1 overexpression (at 80 hours post fertilization; hpf) and is fully evident at 120 hpf. Reducing UHRF1 expression transitions these cells from senescent to proliferation-competent. Removing demonstrated that UHRF1 overexpression at 80 hpf already induced DNA damage response, senescence and decrease of hepatocyte specific pathways and this is further exhanced at 120 hpf.