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

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.

Original languageEnglish
Pages (from-to)1433-1436
Number of pages4
JournalScience
Volume355
Issue number6332
Early online date30 Mar 2017
DOIs
Publication statusPublished - 31 Mar 2017

Keywords

  • 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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