1. Aging increases cell-to-cell transcriptional variability upon immune stimulation
- Author
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Martinez-Jimenez, CP, Eling, N, Chen, H-C, Vallejos, CA, Kolodziejczyk, AA, Connor, F, Stojic, L, Rayner, TF, Stubbington, MJT, Teichmann, SA, de la Roche, M, Marioni, JC, Odom, DT, Chen, Hung-Chang [0000-0002-2849-6752], Connor, Frances [0000-0003-2858-9411], Teichmann, Sarah [0000-0002-6294-6366], de la Roche, Maike [0000-0002-0558-4119], Marioni, John [0000-0001-9092-0852], Odom, Duncan [0000-0001-6201-5599], and Apollo - University of Cambridge Repository
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Aging ,Sequence Analysis, RNA ,Receptors, Antigen, T-Cell ,Genetic Variation ,Lymphocyte Activation ,Mice, Inbred C57BL ,Mice ,Animals ,Single-Cell Analysis ,Transcriptome ,Immunologic Memory ,Cellular Senescence - Abstract
Aging is characterized by progressive loss of physiological and cellular functions, but the molecular basis of this decline remains unclear. We explored how aging affects transcriptional dynamics using single-cell RNA sequencing of unstimulated and stimulated naïve and effector memory CD4(+) T cells from young and old mice from two divergent species. In young animals, immunological activation drives a conserved transcriptomic switch, resulting in tightly controlled gene expression characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging perturbed the activation of this core program and increased expression heterogeneity across populations of cells in both species. These discoveries suggest that increased cell-to-cell transcriptional variability will be a hallmark feature of aging across most, if not all, mammalian tissues.
- Published
- 2017