Fig. 4: Age-related changes in (epi)-transcriptomic programs in mammary stromal cells. | Nature Aging

Fig. 4: Age-related changes in (epi)-transcriptomic programs in mammary stromal cells.

From: Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer

Fig. 4

a,b, UMAP visualization of stromal cell clusters captured by scRNA-seq (a) and snATAC-seq (b). The number of significant DE genes detected by single-cell and pseudobulk analysis with age (a) and DA peaks with age (b) is shown per cell cluster. c, Example of DE gene with DA peak in fibroblast clusters in 3M versus 18M mice. Left: log-normalized values are shown for individual cells (Welch two-sample t-test; ***P = 1.32 × 10−4; cells with zero counts were excluded), along with a pie chart depicting the percentage of expressing cells versus non-expressing cells. Right: pseudobulk snATAC-seq tracks in 3M versus 8 M mice are shown, along with gene structures and significant DA peaks with corresponding log2FC values. d,e, UMAP visualization of fibroblast subclusters Fib-C0–C5 captured by scRNA-seq (d), along with expression of canonical marker genes (e). The proportions of cells from 3M and 18M mice are shown on the right. f, Differences in cell number ratios with age (18M/3M) per fibroblast subclusters captured by scRNA-seq (n = 6; two-sided t-test; **PFib-C2 = 0.0028, **PFib-C0 = 0.0081, *PFib-C4 = 0.043; NS, not significant; boxplots: center line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, replicates). g,h, Expression of marker genes in fibroblast subclusters captured by scRNA-seq. i, log-normalized counts of Cdkn1a in fibroblasts with age (two-sided t-test; ****P = 1.2 × 10−13; cells with zero counts were excluded). j, log-normalized counts of Cdkn1a in fibroblast subclusters with age with feature axis on log scale (two-sided t-test; ****PFib-C0 = 9.1 × 10−8, ****PFib-C2 = 3.8 × 10−9, *PFib-C3 = 0.012; NS, not significant; cells with zero counts were excluded). k, Senescence gene signatures in 3M versus 18M mice across fibroblast subclusters (one-sided t-test; ****PFib-C0 = 2.7 × 10−12, ****PFib-C2 = 5.1 × 10−20, ****PFib-C3 = 3.5 × 10−14, ****PFib-C4 = 1.4 × 10−20, ****PFib-C5 = 3.5 × 10−14). l, Top DE genes with age across replicates from pseudobulk scRNA-seq data for indicated fibroblast subclusters (with >100 cells per age). See also Extended Data Fig. 5 and Supplementary Table 4.

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