UHRF1 overexpression generates distinct senescent states with different Tp53 dependencies.

UHRF1 overexpression in zebrafish liver induces diverse senescent states with distinct Tp53 dependencies, revealing epigenetic influences on senescence phenotypes.

• Why it matters: Understanding how epigenetic regulators like UHRF1 shape senescence is crucial because senescence can either suppress or promote tumor development, impacting cancer therapies and progression.
• What they did: The study used a zebrafish model with UHRF1 overexpression in hepatocytes, analyzing DNA damage, methylome changes, and cell populations via scRNAseq, identifying senescent cells with varying UHRF1 levels.
• The result: High UHRF1 levels produce senescent cells resistant to apoptosis and targeted by senolytics, while low UHRF1 levels allow proliferation in Tp53 mutant backgrounds, highlighting UHRF1’s role in phenotypic diversity.