Induction of reporter expression in Hey2-CreERT2, Rosa26-ZsGreen mice reveals that Hey2 is predominantly expressed in dermal papilla (DP) cells in skin. Lineage tracing of these HEY2⁺ cells during wound healing indicates that HEY2⁺ cells exhibit stemness properties and can contribute to the regeneration of dermal cells.

Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2-CreERT2 knockin mice and crossed them with Rosa26-ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen⁺ cells in the regenerated dermis. We conclude that the HEY2⁺ DP cells and dermal cells exhibit some stemness properties and can contribute to the dermal cell regeneration during wound healing.