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Assessing the effects of aging on the liver endothelial cell landscape using single-cell RNA sequencing
Dongliang Wang1, Mengke Li, Jie Ling
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Hepatology Communications
|February 1, 2023
Summary
Aging impairs liver endothelial cell (EC) function, with new subtypes identified in aged mice. These aged ECs are linked to inflammation and altered differentiation, offering insights into liver aging mechanisms.
Area of Science:
- Vascular Biology
- Aging Research
- Molecular Mechanisms of Disease
Background:
- Endothelial cell (EC) function is critical for vascular health and declines with age, contributing to vascular diseases.
- The specific molecular changes in liver ECs during aging remain poorly understood.
- Aging impacts ECs, influencing vascular integrity and disease susceptibility.
Purpose of the Study:
- To investigate the molecular regulatory mechanisms of liver ECs in aged mice using single-cell RNA sequencing.
- To identify novel EC subtypes associated with aging and their functional implications.
- To elucidate the impact of aging on EC differentiation pathways and intercellular communication in the liver.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) to profile liver EC transcriptomes in young and aged mice.
- Identification and characterization of distinct EC subtypes, including age-specific populations.
- Gene ontology analysis, double immunostaining, pseudo-temporal trajectory analysis, and intercellular communication analysis.
Main Results:
- Eight distinct EC subtypes were identified, with two novel subtypes, aged capillary ECs (Aged ECs) and pro-inflammation capillary ECs (Proinfla.ECs), specifically expressed in aged mice.
- Aged ECs and Proinfla.ECs are associated with inflammatory responses.
- Proliferating capillary ECs (Prolife.ECs) were most affected by senescence, exhibiting altered differentiation pathways in aged mice, potentially promoting angiogenesis and tumorigenesis.
- Intercellular communication analysis revealed increased inflammatory activation in aged liver ECs.
Conclusions:
- This study provides a comprehensive single-cell transcriptomic atlas of liver ECs in young versus aged mice.
- Novel EC subtypes and altered differentiation pathways in aged liver ECs are identified, offering new insights into liver aging.
- The findings highlight the role of inflammation and specific EC subtypes in the aging liver, suggesting potential therapeutic targets for age-related vascular dysfunction.
