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

Autor: 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
Jazyk: angličtina
Předmět:
Popis: 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.
Databáze: OpenAIRE