On the mechanisms of epidermal stemness and differentiation.

High Wnt and low Notch activities characterize epidermal stem cells (SCs), while low Wnt and high Notch activities characterize the terminally differentiated epidermal cells (TDCs). However, the mechanism by which transit amplifying cells (TACs) are induced to become terminally differentiated remains unclear. Our analysis suggests that oscillations in Wnt, Notch, and YAP/TAZ activities lead to the production of TDCs from TACs. Furthermore, the role of stem cell markers in epidermal differentiation, regeneration, and the functional aspects of the epidermis remains unclear. Here, based on the ability of the epidermal SCs to induce the differentiation of TACs, we characterize the SCs as having the expression of Notch ligand, Delta, higher than a critical value. Further, we have functionally defined the critical value of the Delta expression by SCs. Our paper may have general implications for the stemness and differentiation of other tissues.