Deciphering the impact of aging on splenic endothelial cell heterogeneity and immunosenescence through single-cell RNA sequencing analysis.

IF 5.2 2区医学 Q1 GERIATRICS & GERONTOLOGY

Immunity & Ageing Pub Date : 2024-07-18 DOI:10.1186/s12979-024-00452-1

Yanjing Huang, Zhong Liu, Mengke Li, Dongliang Wang, Jinguo Ye, Qiuling Hu, Qikai Zhang, Yuheng Lin, Rongxin Chen, Xuanwei Liang, Xingyi Li, Xianchai Lin

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引用次数: 0

Abstract

Background: Aging is associated with significant structural and functional changes in the spleen, leading to immunosenescence, yet the detailed effects on splenic vascular endothelial cells (ECs) and their immunomodulatory roles are not fully understood. In this study, a single-cell RNA (scRNA) atlas of EC transcriptomes from young and aged mouse spleens was constructed to reveal age-related molecular changes, including increased inflammation and reduced vascular development and also the potential interaction between splenic endothelial cells and immune cells.

Results: Ten clusters of splenic endothelial cells were identified. DEGs analysis across different EC clusters revealed the molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the loss in vascular development function of aged ECs. Notably, four EC clusters with immunological functions were identified, suggesting an Endothelial-to-Immune-like Cell Transition (EndICLT) potentially driven by aging. Pseudotime analysis of the Immunology4 cluster further indicated a possible aging-induced transitional state, potentially initiated by Ctss gene activation. Finally, the effects of aging on cell signaling communication between different EC clusters and immune cells were analyzed.

Conclusions: This comprehensive atlas elucidates the complex interplay between ECs and immune cells in the aging spleen, offering new insights into endothelial heterogeneity, reprogramming, and the mechanisms of immunosenescence.

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通过单细胞 RNA 测序分析破解衰老对脾脏内皮细胞异质性和免疫衰老的影响

背景：衰老与脾脏结构和功能的显著变化有关，会导致免疫衰老，但对脾脏血管内皮细胞（ECs）的详细影响及其免疫调节作用还不完全清楚。本研究构建了小鼠年轻脾脏和衰老脾脏血管内皮细胞转录组的单细胞RNA（scRNA）图谱，以揭示与年龄相关的分子变化，包括炎症增加和血管发育减少，以及脾脏内皮细胞和免疫细胞之间的潜在相互作用：结果：发现了 10 个脾脏内皮细胞群。对不同内皮细胞集群的 DEGs 分析表明，随着年龄的增长，内皮细胞的分子会发生变化，显示出整体炎症微环境的增加以及老化内皮细胞血管发育功能的丧失。值得注意的是，研究发现了四个具有免疫功能的内皮细胞集群，这表明衰老可能导致内皮细胞向免疫样细胞转化（EndICLT）。对免疫学4集群的伪时间分析进一步表明了可能由Ctss基因激活引发的衰老诱导的过渡状态。最后，分析了衰老对不同EC群和免疫细胞之间细胞信号交流的影响：该综合图谱阐明了衰老脾脏中EC和免疫细胞之间复杂的相互作用，为内皮异质性、重编程和免疫衰老机制提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY

CiteScore

10.20

自引率

3.80%

发文量

期刊介绍： Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.