Defining Stem Cell Dynamics and Migration During Wound Healing in Mouse Skin Epidermis

The study investigated stem cell dynamics and migration during wound healing in mouse skin epidermis, identifying two distinct epithelial compartments: a proliferative hub and a migrating leading edge (LE). It was found that stem cell proliferation, migration, and differentiation could be uncoupled during early wound repair stages, with progenitors initially dividing rapidly but depleting, while stem cells became active to generate new progenitors. The LE expressed genes related to cell migration and extracellular matrix remodeling, with metalloproteinases highly upregulated. The study highlighted the role of urokinase and plasminogen activator in blood clot remodeling and showed that the LE had a unique gene expression signature independent of cell proliferation. Clonal analysis revealed that stem cells in the interfollicular epidermis contributed to wound healing by producing progeny that migrated towards the wound edge. The findings suggested that the regenerative stage involved increased proliferative activity of a minority of stem cells, maintaining the fate behavior and lineage relationship of stem cells and progenitors. The study provided insights into the molecular and cellular mechanisms underlying wound healing, emphasizing the transient nature of the LE structure and its distinct gene expression profile.