Spatiotemporal transcriptomics characterizes immune microenvironment during mouse liver aging

Recently, the liver's immunological functions have gradually been unveiled: combating pathogens and maintaining tissue homeostasis. Age-related functional alterations in these immune cells emerge as potential drivers of hepatic dysfunction and age-associated pathologies.

However, systematic investigations into spatiotemporal immune cell dynamics during liver aging remain limited. To address this gap, we analyzed young and old mouse livers using single-cell/nuclei and spatial transcriptomics, revealing T cells as the immune cell population with the most pronounced transcriptomic alterations, marked by enrichment of exhausted CD8+ T cells in aged livers. Spatial mapping showed exhausted CD8+ T cells accumulating in portal vein (PV) zone, co-localizing with periportal hepatocytes (PP hepatocytes).