An atlas of gene regulatory networks for T memory cells in youth and old age
Wayman, J. A.; Thomas, A.; Bejjani, A. T.; Katko, A.; Almanan, M.; Godarova, A.; Korinfskaya, S.; Cazares, T. A.; Yukawa, M.; Kottyan, L. C.; Barski, A.; Chougnet, C. A.; Hildeman, D. A.; Miraldi, E. R.
Show abstract
Aging profoundly affects immune-system function, promoting susceptibility to pathogens, cancers and chronic inflammation. We previously identified a population of IL-10-producing, T follicular helper-like cells ("Tfh10"), linked to suppressed vaccine responses in aged mice. Here, we integrate single-cell (sc)RNA-seq, scATAC-seq and genome-scale modeling to characterize Tfh10 - and the full CD4+ memory T cell (CD4+TM) compartment - in young and old mice. We identified 13 CD4+TM populations, which we validated through cross-comparison to prior scRNA-seq studies. We built gene regulatory networks (GRNs) that predict transcription-factor control of gene expression in each T-cell population and how these circuits change with age. Through integration with pan-cell aging atlases, we identified intercellular-signaling networks driving age-dependent changes in CD4+TM. Our atlas of finely resolved CD4+TM subsets, GRNs and cell-cell communication networks is a comprehensive resource of predicted regulatory mechanisms operative in memory T cells, presenting new opportunities to improve immune responses in the elderly.
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