Aging increases cell-to-cell transcriptional variability upon immune stimulation

Celia Pilar Martinez-Jimenez, Nils Eling, Hung-Chang Chen, Catalina A Vallejos, Aleksandra A Kolodziejczyk, Frances Connor, Lovorka Stojic, Timothy F Rayner, Michael J T Stubbington, Sarah A Teichmann, Maike de la Roche, John C Marioni, Duncan T Odom

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1433-1436
Number of pages4
Issue number6332
Early online date30 Mar 2017
Publication statusPublished - 31 Mar 2017


  • Aging/genetics
  • Animals
  • CD4-Positive T-Lymphocytes/immunology
  • Cellular Senescence/genetics
  • Genetic Variation
  • Immunologic Memory/genetics
  • Lymphocyte Activation/genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Antigen, T-Cell/metabolism
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Transcriptome


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