Hepatocyte CD44 in aged mouse liver correlates with immune modulation and fibrotic priming
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE309965 | GEO | 2026/02/18
REPOSITORIES: GEO
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Project description: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 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 mouse patterns. Spatially, CDKN1A+ hepatocytes localized periportally, while SERPINE1+ aging-associated hepatocytes formed spatial clusters potentially mediated by Claudins and THBS1. Fibrotic regions contained CXCL12+ senescent fibroblasts interacting with CXCR4+ immune cells. Chemotherapy intensified senescence in hepatocytes by five-fold relative to aging, and led to unique CDKN2A+ populations. Across conditions, senescent cells shared AP-1 activation, pro-inflammatory cytokines, and apoptosis resistance, suggesting therapeutic opportunities.
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