Stem cells expand potency and alter tissue fitness by accumulating diverse epigenetic memories (scRNA-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. Overall design: We use single cell RNA-seq technology to delineate transcriptional states across homeostatic, wound-induced and niche-adapted stem cell populations in the skin in vivo. Temporal analysis reveals key genes that change over time as cells initiate and resolve plasticity, and as cells adapt to a new microenvironment.