Abstract The epidermis forms an essential barrier to the outside world. To accomplish this, it contains proliferative stem cells that replenish the tissue, giving rise to differentiated cells that form a functional barrier. We have found that the differentiated cells of the epidermis play an important role in regulating the behavior of their parental stem cells, making them not only descents of the stem cells but part of their regulatory niche. Moreover, the mechanical status of differentiated cells, namely their contractility, is a strong input into multiple aspects of epidermal stem cell behavior, including proliferation, migration, and cell fate decisions. Here we seek to define the pathways, both mechanical and chemical, by which differentiated epidermal cells control both stem cell behavior and skin physiology. Defining the niche components and the mechanisms by which they influence epidermal stem cell behavior is essential to allow manipulation of stem cells for regenerative therapies and/or treatment of diseases that result from stem cell dysregulation.