Single cell-resolved cellular, transcriptional, and epigenetic changes in mouse T cell populations linked to age- associated immune decline

• 成果类型: Article
• 署名作者: He, Jing; Burova, Elena; Taduriyasas, Chandrika; Ni, Min; Adler, Christina; Wei, Yi; Negron, Nicole; Xiong, Kun; Bai, Yu; Shavlakadze, Tea; Ioffe, Ella; Lin, John C.; Ferrando, Adolfo; Glass, David J.
• 署名单位: Regeneron
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11976
• DOI: 10.1073/pnas.2425992122
• 发表日期: 2025-04-08
• 关键词: gene-expression; effector; mice; differentiation; reveals; accessibility; activation; signature; chromatin; subsets

摘要

Splenic T cells are pivotal to the immune system, yet their function deteriorates with age. To elucidate the specific aspects of T cell biology affected by aging, we conducted a comprehensive multi-time point single-cell RNA sequencing study, complemented by single-cell Assay for Transposase Accessible Chromatin (ATAC) sequencing and single-cell T cell repertoire (TCR) sequencing on splenic T cells from mice across 10 different age groups. This map of age-related changes in the distribution of T cell lineages and functional states reveals broad changes in T cell function and composition, including a prominent enrichment of Gzmk+ T cells in aged mice, encompassing both CD4+ and CD8+ T cell subsets. Notably, there is a marked decrease in TCR diversity across specific T cell populations in aged mice. We identified key pathways that may underlie the perturbation of T cell functions with aging, supporting cytotoxic T cell clonal expansion with age. This study provides insights into the aging process of splenic T cells and also highlights potential targets for therapeutic intervention to enhance immune function in the elderly. The dataset should serve as a resource for further research into age-related immune dysfunction and for identifying potential therapeutic strategies.