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

Martinez-Jimenez, CP; Eling, N; Chen, H-C; Vallejos, CA; Kolodziejczyk, AA; Connor, F; Stojic, L; ... Odom, DT; + view all (2017) Aging increases cell-to-cell transcriptional variability upon immune stimulation. Science , 355 (6332) pp. 1433-1436. 10.1126/science.aah4115. Green open access

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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.

Type: Article
Title: Aging increases cell-to-cell transcriptional variability upon immune stimulation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aah4115
Publisher version: http://doi.org/10.1126/science.aah4115
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1555510
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