Cellular senescence in human liver under normal aging and cancer.

ABSTRACT: Cellular senescence, a stress-induced program causing stable cell-cycle arrest, is a hallmark of liver aging, fibrosis, and cancer. However, the cell-type-specific mechanisms, spatial organization, and cancer-associated alterations in the liver remain unclear. We profiled 43 normal human livers spanning ages and fibrosis stages using a single-cell multiome, Xenium spatial transcriptomics, and CODEX, complemented by fibrotic mouse models and 24 colorectal cancer liver metastases. We found CDKN1A+ senescent hepatocytes, fibroblasts, cholangiocytes, and endothelial cells associated with age, liver disease, or cancer. Senescence differed between aged and fibrotic livers, with similar patterns in mice. Spatially, CDKN1A+ hepatocytes localized periportally, while SERPINE1+ aging-associated hepat

SUBMITTER: Karpova A 

PROVIDER: S-EPMC12903365 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature