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Tissue stem cells respond to and integrate environmental cues to determine their fate and function. Injury induces radical changes in the microenvironment that trigger stem cells to undergo a multitude of choreographed experiences that include departing their original niche, migrating into a wound bed, overcoming inflammation, generating tissue de novo, and taking up residence at the new site. Wounds can also induce plasticity, mobilizing stem cells to repair related but different tissues. It remains unclear whether stem cells accumulate and retain memories of these spatially and temporally defined experiences in injury repair, and if so, how this happens and what the consequences are.

Within the hair follicle (HF), bulge stem cells (HFSCs) normally only make hair, but they become repurposed when a wound damages the overlying skin tissue. Using lineage tracing, we monitored …