Systematic profiling reveals distinct senescence signatures and regulators across human brain cell types.

ABSTRACT: Cellular senescence contributes to age-related neurodegeneration, yet its manifestation varies across brain cell types and senescence-inducing stressors. Here, we investigated senescence hallmarks in five human brain cell lines - astrocytes, endothelial cells, microglia, oligodendrocytes, and dopaminergic-like neurons - using chronic 5-Bromodeoxyuridine treatment and validated our findings in primary cells and alternative toxin-induced models. Principal component analysis and transcriptional network inference identified both common and cell-type-specific senescence-associated transcriptional regulators (SATRs). Functional studies of TFAP4, a key SATR, revealed its role in modulating senescence phenotypes in a cell-type-dependent manner, with decreased TFAP4 expression observed in Parkinson

SUBMITTER: Russo T 

PROVIDER: S-EPMC12698866 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature