Fig. 6: Gain of lymphocyte innateness in memory T cells is a common age-associated transcriptional signature.

Pseudobulk differential expression of single-cell sequencing data from young (Y) and older (O) adults within each antigen specificity were compared, and differentially expressed genes (DEGs) were identified (see also Supplementary Fig. 7D). Only antigen-specific memory T cells were selected, and stem-like cells (see Fig. 5A) were excluded from consecutive analyses. A, B Number of unique (A) and shared (B) DEGs from O versus Y comparisons. C Heatmap and K-means clustering of DEGs identified in Supplementary Fig. 7D. Selected genes in each K-means cluster are listed on the right. D Pathway and annotation enrichment analysis of DEGs in K-means cluster 1. One-sided Fisher’s exact tests with Benjamini-Hochberg correction were used for statistical analyses. For enrichment analyses of other K-means clusters, see Supplementary Fig. 7E. No enrichments were found for K-means clusters 5 and 6. E Gene set enrichment analyses in single-cell sequencing data based on pseudobulk expression analyses of antigen-specific memory T cells comparing Y and O groups. For statistical analyses, see “Methods”. The lymphocyte innateness gene set was initially collated by Gutierrez-Arcelus et al.³⁶. NES, normalized enrichment score.