Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

STEM CELLS AND Renewal IN EPITHELIAL TISSUES
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in case of damage. A dramatic effect is seen if large numbers of hepatocytes are
removed surgically or are killed by poisoning with carbon tetrachloride. Within
a day or so after either sort of damage, a surge of cell division occurs among the
surviving hepatocytes, quickly replacing the lost tissue. If two-thirds of a rat’s liver
is removed, for example, a liver of nearly normal size can regenerate from the
remainder by hepatocyte proliferation within about two weeks.
Both the pancreas and the liver contain small populations of stem cells that
can be called into play as a backup mechanism for production of the differentiated
cell types in more extreme circumstances. This imparts resilience to the
mechanisms of renewal and repair.
Some Tissues Lack Stem Cells and Are Not Renewable
The variety among tissues in the capacity for self-renewal is illustrated in a striking
way by comparing the olfactory epithelium in the nose, the auditory epithelium
of the inner ear, and the photoreceptive epithelium of the retina. These three sensory
structures, which like the epidermis develop from the ectodermal layer of
the early embryo, differ radically in their self-renewal capabilities. The olfactory
epithelium contains a population of stem cells that give rise to differentiated cells
that have a limited life-span and are continually replaced. But unlike the epidermis,
these differentiated cells (the olfactory receptor cells) are neurons, with cell
bodies lying in the olfactory epithelium and axons that extend back to the olfactory
lobes in the brain. The continual renewal of this epithelium therefore involves
continual production of fresh axons, which have to navigate back to the appropriate
sites in the brain.
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.
Summary
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.