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

ABSTRACT: Heterogeneity is largely attributed to distinct genetic changes within each cell population but the widespread epigenome repatterning that characterizes most cancers is also highly heterogenous within tumors, and can generate cells with diverse identities and malignant features. 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. Deletion of tp53 from UHRF1 overexpressing line completely rescued cellular senescence and some of the key senescence-associated genes but do not abrograte the major transcriptomic changes caused by UHRF1 overexpression.

ORGANISM(S): Danio rerio

PROVIDER: GSE302812 | GEO | 2026/08/25

REPOSITORIES: GEO