Injury Response
Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. By studying diverse cell types within the skin, we have discovered that each cell type leverages distinct cellular behaviors to maintain architecture and function.
The cell type we have historically focused on, epidermal stem cells, maintains cell density in the face of neighboring cell loss by locally coordinating proliferation and differentiation (Mesa*, Kawaguchi*, Cockburn* 2018).
In contrast, tracking the same dermal fibroblasts over time in live mice revealed that while individual fibroblasts have remarkably stable positions in homeostasis, neighboring cells respond to local cell loss by extending their membranes into the depleted space (Marsh 2018).
More recently, studying endothelial cells in the dermal vasculature has revealed that upon neighboring cell loss, endothelial cells reactivate migratory and self-repair behaviors to maintain overall vascular architecture and function (Kam 2023).
Thus, by comparing across various skin cell types, we are discovering the behavioral flexibility that allows architectural and functional maintenance of each tissue, setting the stage for future studies of tissue cross-talk in skin regeneration.
When mammalian skin undergoes repair on a larger scale, cells respond by migrating and proliferating to close the wound. To understand the coordination of cellular repair behaviors and their effects on homeostatic functions in a live mammal, we 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.
Mosaic image of 1mm wound at day 0 and day 9 after wounding.
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, leads to effective reconstruction of the epithelial tissue and the extent to which homeostatic processes such as differentiation and proliferation are affected during the repair process.
Timelapse movie 3 days post wound induction of skin epithelial nuclei (cell) migration.
Collectively, our studies have revealed 1) that both stem cells and differentiated cells migrate and functionally participate in wound repair, 2) that cells depart from a highly proliferative zone by directionally dividing towards the wound while collectively migrating, 3) that proliferation functions to pattern and restrict the recruitment of undamaged cells (Park, 2017).