Tissue stem cells: survival of the fittest

Abstract

Barrier epithelial tissues such as the skin, lung and gut are the first line of defense between our body and the outside world. As such, their stem cells must continually generate and rejuvenate their tissue, but also self‐renew to maintain the reservoir of stem cells. When the barrier has been breached, for example by wounding, the stem cells must not only repair the damaged tissue but also call to the immune system to help guard against pathogen entry. All the while the stem cells must protect themselves from a variety of assaults, including not only injury but also mechanical stress, noxious chemicals, ultraviolet radiation, and allergens that stimulate an inflammatory response. How do stem cells equip themselves to respond to these different stresses? My laboratory uses mice as a model organism and the skin epithelium as our tissue to explore the molecular mechanisms involved. We use high throughput genetic and genomic approaches to learn at a molecular level how the stem cells balance growth and differentiation in normal tissue homeostasis, and how they change their behavior and interactions with their neighbors (the stem cell ‘niche’) in response to changes in their environment. Our global objective is to apply our knowledge of the basic science of epithelial stem cells to unfold new avenues for therapeutics to treat inflammatory conditions and cancers.