Finding one's niche in the skin

Abstract

Skin epithelia must rejuvenate constantly during normal homeostasis and repair damage after wounding. Fulfilling these roles necessitates reservoirs of stem cells that persist for life. This review focuses on the elusive stem cell niche of the epidermis, long thought to reside within the basal layer that is sandwiched between the basement membrane and the suprabasal interface.

Figure 1. The Architecture of the Basal-to-Spinous Switch

The proliferative basal cells of the epidermis adhere to an underlying basement membrane, separating the dermis from the epidermis, and differentiate into spinous cells in the suprabasal layer. Integral to this switch are epigenetic changes in chromatin and Notch signaling, which are activated in spinous cells. Notch is thought to be repressed in basal cells by several mechanisms, including the Notch inhibitor Numb, which is frequently asymmetrically inherited after basal cell division. In turn, Notch signaling downregulates integrin and p63 gene expression and, in conjunction with AP2s, activates C/EBP expression. Models of how asymmetric divisions could promote the basal-to-spinous switch are depicted. Epidermal drawing by Ann Canapary.