Stem cell dynamics and heterogeneity: implications for epidermal regeneration and skin cancer.

The skin epithelium undergoes constant renewal, a process that is driven by stem cells (SCs) localising to the interfollicular epidermis and different regions of the hair follicle. Over the last years, tremendous progress has been made to unravel the physiological function of distinct stem and progenitor cell populations by using genetic lineage tracing in vivo, transplantation, clonogenicity approaches and live cell imaging. It turned out that these cell compartments constitute heterogeneous SC pools and that individual SCs respond differently to various signals sent by the microenvironment. Recent genetic manipulation experiments and elegant mouse models have shed light on the signalling pathways being crucial for self-renewal and lineage fate decisions during tissue homeostasis. Here, we summarise current concepts of SC function in mammalian skin and focus on the dynamic behaviour of SCs during morphogenesis and tissue regeneration of the skin epithelium. Clearly, understanding the cellular and molecular mechanisms of SC regulation and function during tissue homeostasis has enormous impact on our view of the pathogenesis of various skin diseases and will be beneficial for regenerative medicine. Recent experiments suggest an important role of tissue SCs in the process of skin tumour initiation and progression. For the future, the genuine challenge is to further dissect SC function in pathophysiological settings and to translate our knowledge to design novel efficient therapeutic strategies for treatment of cutaneous cancer.