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Spatiotemporal Transcriptomics Characterizes Immune Microenvironment During Mouse Liver Aging
Jiahua Lu1,2, Yuqian Wang3, Wenxue Zhao4
1Department of Pathology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Aging Cell
|April 21, 2026
Summary
Liver aging drives T cell exhaustion, particularly CD8+ T cells, in the portal vein zone. Targeting LPIN1 in hepatocytes may offer new therapies for age-related liver diseases.
Area of Science:
- Immunology
- Hepatology
- Gerontology
Background:
- The liver performs metabolic and immunological functions, crucial for homeostasis.
- Age-related changes in liver immune cells contribute to dysfunction and disease.
- Limited understanding of immune cell dynamics during liver aging.
Purpose of the Study:
- Investigate spatiotemporal immune cell dynamics in aging mouse livers.
- Identify immune cell populations with significant age-related transcriptomic changes.
- Explore mechanisms linking liver aging, T cell exhaustion, and disease.
Main Methods:
- Single-cell/nuclei and spatial transcriptomics on young and old mouse livers.
- Analysis of T cell populations and their spatial distribution.
- Investigation of hepatocyte-specific gene expression (LPIN1).
Main Results:
- T cells exhibited the most pronounced transcriptomic alterations with age.
- Aged livers showed enrichment of exhausted CD8+ T cells in the portal vein zone.
- LPIN1 upregulation in periportal hepatocytes promoted CD8+ T cell exhaustion, linked to disease progression.
Conclusions:
- Exhausted CD8+ T cells accumulate in aged livers, particularly near portal veins.
- LPIN1 in hepatocytes is a key factor promoting T cell exhaustion.
- Targeting LPIN1 presents a potential therapeutic strategy for age-related liver diseases.
