Fig. 5: Aging is associated with a progressive increase of chromatin accessibility in HSCs.
a Principal component analysis of ATAC-seq data from stem- and progenitor cells, from juvenile, adult, and old mice (nJCD49b– = 5 samples, nJCD49b+ = 5 samples, nJLMPP = 6 samples, nJGMP = 4 samples, nACD49b– = 5 samples, nACD49b+ = 5 samples, nALMPP = 5 samples, nAGMP = 5 samples, nOCD49b– = 5 samples, nOCD49b+ = 5 samples, nOLMPP = 3 samples, nOGMP = 4 samples). b Principal component analysis of ATAC-seq data from CD49b– and CD49b+ HSC subsets, from juvenile, adult, and old mice. (nJCD49b– = 5 samples, nJCD49b+ = 5 samples, nACD49b– = 5 samples, nACD49b+ = 5 samples, nOCD49b– = 5 samples, nOCD49b+ = 5 samples). c Heatmap (left) of row normalized chromatin accessibility for regions with differential accessibility (padj <0.0001, Wald test) between juvenile and old CD49b– and/or between juvenile and old CD49b+ cells. Regions are divided into three clusters based on hierarchical clustering. Median normalized chromatin accessibility of clusters 1–3 is shown (right). d Percentage of regions constituting open chromatin in clusters 1–3. e Top 5 GO biological processes significantly enriched in clusters 1–3. f Transcription factors with enriched binding motifs (-ln(p-value)>50) in clusters 1–3. g Venn diagram of regions with differential accessibility (padj <0.0001, Wald test) in old compared to juvenile HSCs (Old vs. Juvenile) or in adult compared to juvenile HSCs (Adult vs. Juvenile). h Transcription factors with enriched binding motifs (-ln(p-value)>10) in regions with increased or decreased accessibility in both adult and old compared to juvenile HSCs. A one-sided binomial test was used to determine significance in e, f, and h. p-values in c and e were adjusted using the Benjamini–Hochberg method. Boxplots show the distribution in each population (center line, median; box limits, interquartile range; whiskers, furthest data point within 1.5x of the interquartile range). J juvenile, A adult, O old. See also Supplementary Figs. 7–9. Source data are provided as a Source Data file.
