Ontogeny and Homeostasis of Adult Epithelial Skin Stem Cells

Mouse epithelial skin stem cells constitute an important model system for understanding the dynamics of stem cell emergence and behavior in an intact vertebrate tissue. Recent published work defined discrete populations of epithelial stem cells in the adult skin epithelium, which reside in the hair follicle bulge and germ, isthmus, sebaceous gland and inter-follicular epidermis. Adult epidermal and hair follicle stem cells seem to adopt mostly symmetric or unidirectional fate decisions of either one of two possible fates: (1) differentiate and be lost from the tissue or (2) expand symmetrically to self-renew. Asymmetric divisions appear to be mostly implicated in differentiation and stratification of the epidermis. While mechanisms of adult stem cell homeostasis begin to be unraveled, the embryonic origin of the adult epithelial skin stem cells is poorly understood. Recent studies reported Sox9, Lgr6, and Runx1 expression in subpopulations of cells in the embryonic hair placode. These subpopulations seem to act as precursors of different classes of adult epithelial stem cells. In particular, Runx1 regulates a Wnt-mediated cross-talk between the nascent adult-type hair follicle stem cells and their environment, which is essential for timely stem cell emergence, proper maturation, long-term differentiation potential, and maintenance. The new data begin to define the basic dynamics and regulatory pathways governing the ontogeny of adult epithelial stem cells.