Grant: Project Grant

The epidermis is the outermost layer of our skin. It forms an essential barrier between our bodies and the outside environment, protecting us from pathogens, UV radiation, and other external insults. As part of this protective function, we shed approximately 3 billion terminally differentiated epidermal cells from the skin's surface every day. These cells are replaced by steady supply of new ones that are generated by a population of resident epidermal stem cells. We know very little about how this replacement process is controlled. For instance, how do stem cells know how many differentiating cells to make? What causes them to make more (or less) differentiated cells in response to different types of injuries and stresses? We hypothesize that stem cells and differentiating cells talk to one another, sending messages that control when, where, and how often differentiation occurs. To test this hypothesis, we will use microscopy to watch cells in the living skin as they differentiate in real time. In our first aim, we will test whether stem cells produce a key message on their cell surface that instructs their neighbors to start differentiating. In our second aim, we will investigate whether cells that have started to differentiate can change their mind, and whether this may be controlled by the loss of nearby cells after damage from UV radiation. Our ultimate goal is to build a picture of how stem cells pattern their decisions to match supply with demand during tissue regeneration.