In Chapters 7 and 21, we saw how the various cell types become different in the embryo and how cell memory and signals from their neighbors enable them to remain different thereafter. In Chapter 19, we discussed the technology used to build multicellular tissues—the devices that bind cells together and the extracellular materials that give them support. But the adult body is not static: it is a structure in dynamic equilibrium, where new cells are continually being born, differentiating, and dying. Homeostatic mechanisms maintain a proper balance, so that the tissue architecture is preserved despite the constant replacement of old cells by new. In this chapter, we focus on these developmental processes that continue throughout life. In doing so, we shall illustrate some of the diversity of specialized cell types and see how they work together to perform their tasks.
We shall examine in particular the role played in many tissues by stem cells— cells that are specialized to provide a fresh supply of differentiated cells where these need to be continually replaced, or when they are required in great number for purposes of repair and regeneration. We shall see that while many tissues renew and repair themselves, some others do not; there, lost cells are lost forever, causing deafness, blindness, dementia, and other ills.
In the final section of the chapter, we discuss how stem cells can be generated and manipulated artificially, and we confront the practical question that underlies the current storm of interest in stem-cell technology: How can we use our understanding of the processes of cell differentiation and tissue renewal to improve upon nature, and make good those injuries and failings of the human body that have hitherto seemed to be beyond repair?
Among all the self-renewing tissues in a mammal, the champion—for speed at least—is the lining of the small intestine: the long, convoluted portion of the gut tube that is chiefly responsible for absorption of nutrients from the gut lumen. To introduce stem cells, we take the small intestine as our starting point—not only because it renews itself at a greater rate than any other tissue in the body, but also because the molecular mechanisms that control its organization are particularly well understood. It thereby provides a beautiful illustration of the principles of stem-cell systems that have broad applicability.
FibRoblaStS and theiR tRanSFoRmationS: the ConneCtive-tiSSue Cell Family blood veSSelS, lymphatiCS, and endothelial CellS a hieRaRChiCal Stem-Cell SyStem: blood Cell FoRmation epithelial cell migration from “birth” at the bottom the lining of the Small intestine is Continually Renewed through Cell proliferation in the Crypts
The lining of the small intestine (and of most other regions of the gut) is a sin-gle-layered epithelium, only one cell thick. This epithelium covers the surfaces of the villi that project into the lumen, and it lines the crypts that descend into the underlying connective tissue (Figure 22–1). Dividing cells are restricted to the crypts, and differentiated cells, no longer dividing, pour out of the crypts in a steady stream onto the villi. There are four main types of nondividing differentiated cells—one absorptive and three secretory (Figure 22–2): 1.
Absorptive cells (also called brush-border cells or enterocytes) have densely packed microvilli on their exposed surfaces. Their job is to take up nutrients from the gut lumen. To this end, they also produce hydrolytic enzymes that perform some of the final steps of extracellular digestion. They are the majority cell type in the epithelium.
2.
Goblet cells secrete mucus into the gut lumen that covers the epithelium with a protective coat.
3.
Paneth cells form part of the innate immune defense system (discussed in Chapter 24) and secrete proteins that kill bacteria.
4.
Enteroendocrine cells, of more than 15 different subtypes, secrete serotonin and peptide hormones that act on neurons and other cell types in the gut wall and regulate the growth, proliferation, and digestive activities of cells of the gut and other tissues.