Mechanical Tension Mobilizes Lgr6+ Epidermal Stem Cells to Drive Skin Growth (II)

Uniquely among mammalian organs, skin is capable of dramatic size change in adults, yet the mechanisms underlying this striking capacity are unclear. Here, we utilize a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning-guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of not Lgr5+, but instead Lgr6+ stem cells of the interfollicular epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals. This experiment totally includes 10 samples from mice. We take skin samples from expanded mouse and non-expanded control mice, at four different time points, along with two non-surgery mice skin samples with different hair cycle. The time points including PI-0, PI-7, PI-14, PI-21. PI- means days post-fully injection of the expander. The Telogen is the rest stage of hair cycle, the Anagen is the growth stage of hair cycle. RNA were extracted from whole skin tissue, and subjected for microarray analysis.