Epidermal Stem Cells at a Glance
- The epidermis is a continually renewing tissue the function of which is maintained by a hierarchy of stem cells, transit amplifying cells, and terminally differentiating cells.
- In the proliferative hierarchy, stem cells have the highest proliferative potential.
- Epidermal stem cells may be identified by their functional characteristics, by distinctive cell cycle patterns, or by characteristic proteins.
- Epidermal stem cells usually exist in characteristic proliferative units with little lateral migration.
- The regulation of epidermal stem cells comprises complex pathways many of which are shared by embryonic, morphogenetic, and homeostatic processes.
- Epidermal diseases are associated with or may arise from proliferative dysfunction in the stem cell or transit amplifying cell compartments.
- Epidermal stem cells are attractive targets for cell and gene therapies.
The cutaneous epithelium is a continually renewing tissue maintained in a dynamic equilibrium of proliferation in the basal layer and loss through terminal differentiation from the suprabasal layers. This process is orchestrated with great elegance by a hierarchy of stem cells, transient amplifying cells, and terminally differentiating cells. These populations of cells work together to maintain lifelong tissue function and to bring about tissue repair. This chapter focuses on the role of stem cells and their identification in the epidermis.
Proliferation in the cutaneous epithelium begins with the stem cells.1,2 Stem cells in this regard lack many characteristics of terminal differentiation, and have an intrinsically high proliferative potential relative to the other proliferating cells, but are generally capable of lifelong proliferation.3 Upon division, a stem cell produces off one daughter that remains a stem cell, and one daughter that goes on to produce a series of transit amplifying cells that serve to magnify or amplify the stem cell's division resulting in the production of many differentiated cells with minimal input from the stem cell. This hierarchical system that usually involves decreasing proliferative potential is illustrated in Fig. 45-1. Stem cells typically interact with their surroundings in a supportive, protective niche.1
The proliferative hierarchy in epithelia: the stem cell concept. The ultimate progenitor cells are termed stem cells. They are slow cycling, long-lived, phenotypically undifferentiated, reside in specialized microenvironments, and constitute only a small percentage of the total epithelial cell population. Stem cell division produces transit amplifying or committed progenitor cells, which cycle rapidly and produce a clonal expansion of the offspring arising from an initial stem cell division. These cells eventually become the mature, terminally differentiated cells that constitute the bulk of a given epithelial population. Numbers indicate generation.
Stem cells may be studied by the presence or absence of proteins on their surface that distinguish them from other proliferative cells.2 Such proteins may be internal, or more desirably, proteins on the cell surface that render the cells selective by various methods such as ...