Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories (ATAC-seq)

Immune and tissue stem cells retain an epigenetic memory of inflammation that intensifies sensitivity to future encounters. Here, we address whether and to what consequence stem cells possess and accumulate memories of diverse experiences. Monitoring a choreographed response to wounds, we find that as hair follicle stem cells leave their niche, migrate to repair damaged epidermis and take up long-term foreign residence there, they accumulate long-lasting epigenetic memories of each experience, culminating in post-repair epigenetic adaptations that sustain the epidermal transcriptional program and surface barrier. Each memory has its own physiological impact, collectively endowing these stem cells with heightened regenerative ability to heal wounds and broadening their tissue regenerating tasks compared to their naïve counterparts. These findings have profound implications for tissue fitness and aging. We use ATAC-seq technology to delineate open chromatin states across homeostatic, wound-induced and niche-adapted SC populations in the skin in vivo. By looking at differences in chromatin accessibility through time, we identify regions that open and close as cells undergo plasticity and enter a new niche, including those that correspond to memories of their prior experiences.