Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviors and their effects on homeostatic functions in a live mammal remains unclear. To answer these questions, we have established the ability to track the lifetime of epidermal stem cells and interrogate their behaviors. Thus, we have demonstrated that stem cells do not appear to be intrinsically biased towards either self-renewal or differentiation but instead appear to be influenced by the fate of their sister cells. Additionally, as basal stem cells stochastically commit to differentiation, they transit through the suprabasal differentiated layers by predominately using existing columnar epidermal units (EDUs) (Rompolas*, Mesa*, Science 2016; Figure1).
On the basis of this work we have now developed the ability to monitor tissue repair in real time and captured the spatiotemporal dynamics of individual epithelial behaviors by imaging wound re-epithelialization in live mice (Figure 2).
By tracking cells over time and using a variety of genetic and pharmacological manipulations, we have been able to study how the interplay between repair behaviors, such as migration and proliferation, leads to effective reconstruction of the epithelial tissue and the extent to which homeostatic processes such as differentiation are affected during the repair process (Movie and Figure 3).
We are also studying how these interconnected cellular behaviors result into tissue-scale changes which allowed us to test the functional role not only of individual behaviors but also their spatial organization within the repairing epithelium. Finally, our understanding from relevant cross-talks at place during homeostatic conditions with neighboring populations such as mesenchymal and immune cells among other will provide a tool to dissect the various contributions of relevant cell types to de novo repair and to shed light on the critical cellular and signaling components that are required for tissue repair.