Wounding induces preexisting multinucleated cells to survive and thrive as leader cells

Abstract

Epithelial wounds are repaired through collective cell migration, a process orchestrated by a small subset of leader cells at the wound edge1-3. How these functionally distinct cells arise from an apparently homogeneous population of epithelial cells remains unclear. Here, we show that injury to cultured epithelial sheets allows the survival of multinucleated cells that are otherwise eliminated under normal conditions. We reveal that multinucleated cells preexist prior to injury and extend protrusions toward the wound, eventually adopting leader-like behaviors. These findings identify multinucleated cells as a latent reservoir for leader cell emergence. Our work highlights the inherent heterogeneity of epithelial sheets and uncovers a previously unrecognized function of multinucleated cells during wound healing.