Epigenetic memories inscribed in chromatin accessibility in aged hematopoietic stem cells

Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here, we performed an integrated analysis of transcriptome and chromatin accessibility of aged HSCs and downstream progenitors. Alterations in chromatin accessibility preferentially took place in HSCs with aging, suggesting that the epigenetic memories are imprinted in HSCs. As expected, genes nearest to open differentially accessible regions (DARs) showed significantly higher levels of basal expression in aged HSCs than in young HSCs. Open DARs in aged HSCs showed enrichment of binding motifs of the ATF family, STAT family, and CNC family. Cytokine stimulation induced significantly enhanced higher levels of expression of genes nearest to open DARs in aged HSCs than in young HSCs, suggesting open DARs contribute to augmented transcriptional responses under stress conditions in aged HSCs. Our findings provide key epigenetic insights into HSC aging and serve as a reference for future studies.