The chromatin accessibility signature of human immune aging stems from CD8+ T cells

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programsbehind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptomein PBMCs, purified monocytes, and B and T cells. Analysis of samples from 77 young and elderly donors revealed a novel androbust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated withT cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analysesof chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging andidentified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borneby memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study providesa unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associatedimmunodeficiency.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 5 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001003602	Dataset consisting of: (1) N=234 genome-wide chromatin accessibility (ATAC-seq) profiles for distinct N=21 healthy old and N=28 healthy young subjects. ATAC-seq biological samples provided for the following tissues: PBMC (N=24), CD14+ monocytes (N=18), CD8+ memory T cells (N=7), CD8+ naive T cells (N=7), CD4+ memory T cells (N=7), CD4+ naive T cells (N=7), and naive B cells (N=7). (2) N=39 genome-wide transcription (RNA-seq) data for distinct N=15 healthy old and N=24 healthy young subjects' PBMCs.	Illumina HiSeq 2500	273

Publications	Citations
The chromatin accessibility signature of human immune aging stems from CD8<sup>+</sup> T cells. Ucar D, Márquez EJ, Chung CH, Marches R, Rossi RJ, Uyar A, Wu TC, George J, Stitzel ML, Palucka AK, Kuchel GA, Banchereau J. J Exp Med 214: 2017 3123-3144	105
Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function. Lawlor N, Márquez EJ, Orchard P, Narisu N, Shamim MS, Thibodeau A, Varshney A, Kursawe R, Erdos MR, Kanke M, Gu H, Pak E, Dutra A, Russell S, Li X, Piecuch E, Luo O, Chines PS, Fuchbserger C, NIH Intramural Sequencing Center, Sethupathy P, Aiden AP, Ruan Y, Aiden EL, Collins FS, Ucar D, Parker SCJ, Stitzel ML. Cell Rep 26: 2019 788-801.e6	41
Sexual-dimorphism in human immune system aging. Márquez EJ, Chung CH, Marches R, Rossi RJ, Nehar-Belaid D, Eroglu A, Mellert DJ, Kuchel GA, Banchereau J, Ucar D. Nat Commun 11: 2020 751	228
CoRE-ATAC: A deep learning model for the functional classification of regulatory elements from single cell and bulk ATAC-seq data. Thibodeau A, Khetan S, Eroglu A, Tewhey R, Stitzel ML, Ucar D. PLoS Comput Biol 17: 2021 e1009670	4
Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC. Hu Y, Xu Y, Mao L, Lei W, Xiang J, Gao L, Jiang J, Huang LA, Luo OJ, Duan J, Chen G. Front Aging 2: 2021 797040	1