Dynamic regulation of human epidermal differentiation by adhesive and mechanical forces

The interfollicular epidermis is the multilayered epithelium that forms the outer layer of the skin. It is maintained by stem cells that are attached to a basement membrane, which lies on top of the underlying connective tissue, the dermis. Cells undergo terminal differentiation as they detach from the basement membrane and move toward the outer epidermal surface. Over time, many of the molecular regulators of this process have been identified. It is now is clear that these pathways also receive critical input from the physical properties of the tissue. In this review, we describe how changes in these factors regulate differentiation and how new insights from single cell RNA sequencing could provide validation or challenge to the existing experimental models.