Stem-cell systems are organized in many different ways, but they share some underlying principles. Consider the epidermis, for example—the outer, epithelial covering of the body. The epidermis undergoes continual renewal, but, unlike the lining of the gut, it is multilayered or stratified. Stem cells are located in the basal layer, and their progeny move outward toward the exposed surface, differentiating as they go. They end up as lifeless scales or squames, which are eventually shed from the surface of the skin (Figure 22–10). Even though the architecture of this tissue is very different from that of the intestine, many of the same basic principles apply. The stem cells depend for their existence on signals from a specific niche, in this case the basal lamina and underlying connective tissue. The daughters of stem cells that are committed to differentiation undergo several divisions as transit amplifying cells (while still in the basal layer) before differentiating. Finally, a stochastic independent-choice mechanism dictates the fates of the daughters of a stem-cell division, allowing for increase in the number of stem cells when needed for growth or wound healing. Most of the same signaling pathways that organize the intestinal stem-cell system are also involved in regulating the epidermal stem-cell system, although with different individual roles.
Figure 22–9 How Notch signaling, in combination with Wnt, maintains stem cells and drives cell diversification in the intestine. wnt signaling leads to expression of notch and delta in the cells of the crypt, and delta-notch signaling in the crypt mediates lateral inhibition between adjacent cells. Cells expressing higher levels of delta eventually activate notch in their neighbors, adopt a secretory fate, and stop dividing; their neighbors, with activated notch, are prevented from differentiating and keep on dividing. essentially the same process operates at the crypt base, where the paneth cells express higher levels of delta to prevent stem cells from differentiating, and in the transit amplifying population, where nascent secretory cells express higher levels of delta. division continues in the notch-activated cells as they move up the crypt, until they escape from the influence of wnt and emerge onto the villi to become absorptive cells.
squame about to fake off from surface keratin flaments connective tissue of basal cell basal cell dividing
Figure 22–10 The multilayered structure of the epidermis, as seen in thin skin of a mouse. (a) the epidermis forms the outer covering of the skin, creating a waterproof barrier that is self-repairing and continually renewed. beneath this lies a relatively thick layer of connective tissue, which includes the tough, collagen-rich dermis (from which leather is made) and the underlying fatty subcutaneous layer or hypodermis. the cells of the epidermis are called keratinocytes, because their characteristic differentiated activity is the synthesis of keratin intermediate filament proteins, which give the epidermis its toughness. these cells change their appearance and properties from one layer to the next, progressing through a regular program of differentiation. those in the innermost layer, attached to an underlying basal lamina, are termed basal cells, and it is usually only these that divide: the basal cell population includes relatively small numbers of stem cells along with larger numbers of transit amplifying cells derived from them. above the basal cells are several layers of larger prickle cells, shown in top view in (b), whose numerous desmosomes—each a site of anchorage for thick tufts of keratin filaments—are just visible in the light microscope as tiny prickles around the cell surface. beyond the prickle cells lies the thin, darkly staining granular cell layer, where the cells are sealed together to form a waterproof barrier; this marks the boundary between the inner, metabolically active strata and the outermost layer of the epidermis, consisting of dead cells whose intracellular organelles have disappeared. these outermost cells are reduced to flattened scales, or squames, filled with densely packed keratin, which are eventually shed from the surface of the skin. the time from exit of a cell from the basal layer to its loss by shedding at the surface is a week or two, depending on body region and species.