In contrast, in mammals at least, the auditory epithelium and the retinal epithelium lack stem cells, and their sensory receptor cells—the sensory hair cells in the ear, the photoreceptors in the retina—are irreplaceable. If they are destroyed— whether by too much exposure to loud noise, by looking into the beam of a laser, or through degenerative processes in old age—the loss is permanent.
Many tissues in the adult mammalian body are continually renewed by stem cells. Stem cells, by definition, are not terminally differentiated and have the ability to divide throughout the organism’s lifetime, yielding some progeny that differentiate and others that remain stem cells. The lining of the gut renews itself more rapidly than any other tissue in the mammalian body and provides a paradigm for the workings of stem-cell systems. In the small intestine, there is a continual upward flow from crypts, where new cells are generated by cell division, onto villi that are composed of nondividing differentiated cells. Wnt signaling maintains cell proliferation in the crypts, and overactivation of the Wnt pathway gives rise to tumors. Stem cells lie at each crypt base and are distinguished by expression of Lgr5 and certain other genes. The Lgr5+ stem cells are multipotent, each capable of generating several different types of differentiated cells as well as new stem cells. The balance of fate choices is adjusted according to need, allowing increase in the number of stem cells where more are needed for growth or repair. In a suitable cell-free culture medium, a single Lgr5+ stem cell can generate a self-organizing “minigut,” containing all the standard intestinal epithelial cell types.
Other self-renewing epithelia, such as the epidermis with its multilayered (stratified) architecture, have stem cells and their differentiating progeny arranged in different ways but are governed by similar basic principles. However, tissue renewal and repair does not always have to depend on stem cells. Thus, the population of insulin-producing cells in the pancreas is enlarged and renewed by simple duplication of existing insulin-producing cells. Similarly, in the liver, differentiated hepatocytes remain able to divide throughout life and can dramatically increase their division rate when the need arises. At an opposite extreme, some tissues, such as the sensory epithelia of the ear and the eye, do not undergo any turnover and are not renewable: their cells, once lost, are lost forever.
FibRoblaStS and theiR tRanSFoRmationS:  the ConneCtive-tiSSue Cell Family
From epithelia, with their varied patterns of renewal and their enormous variety of protective, absorptive, secretory, sensory, and biosynthetic functions, we turn now to connective tissues. Connective tissues typically consist of cells dispersed in extracellular matrix that they themselves secrete, as discussed in Chapter 19. They originate from the mesodermal (middle) layer of the early embryo, sandwiched between ectoderm and endoderm (see Chapter 21, Figure 21–3).
In the adult body, virtually all epithelia are supported by a connective-tissue bed, or stroma; and specialized types of connective tissue, such as bone, cartilage, and tendon, form the supporting framework of the body as a whole. No less important than its mechanical role, connective tissue also contains the blood vessels that bring the oxygen and nourishment on which all cells depend. Cells of the immune system roam through connective tissue, passing in and out of blood vessels and lymphatics, and providing defence against infection; and through the meshes of connective tissue run peripheral nerves. Also embedded in connective tissue are the muscles that enable us to move. In these many ways, the cells that form connective tissue and synthesize its various types of extracellular matrix contribute to the support and repair of almost every tissue and organ.