Essential Cell Biology 5th edition

712 CHAPTER 20 Cell Communities: Tissues, Stem Cells, and Cancer
matrix is slowly eaten away by a set of cells called osteoclasts, akin to
macrophages, while new matrix is deposited by another set of cells, osteoblasts,
akin to fibroblasts. New red blood cells are generated continually
by blood-forming precursor cells in the bone marrow; they are released
into the bloodstream, where they recirculate continually for about 120
days before being removed and destroyed by phagocytic cells in the liver
and spleen. In the skin, dead cells in the outer layers of the epidermis are
continually flaking off and being replaced from below, so that the epidermis
is renewed with a turnover time of about two months. And so on.
Our life depends on these renewal processes, as evidenced by our
response to excessive exposure to radiation. In high enough doses, ionizing
radiation blocks cell division and thus halts tissue renewal: within
a few days, the lining of the intestine, for example, becomes denuded of
cells, leading to the devastating diarrhea and water loss characteristic of
acute radiation sickness.
QUESTION 20–6
Why does ionizing radiation stop cell
division?
SELF-
RENEWAL
proliferating
precursor
cells
stem cell
Clearly, there have to be elaborate control mechanisms to keep cell production
and cell loss in balance in the normal, healthy adult body. Cancers
originate through violation of these controls, allowing rare mutant cells
in the self-renewing tissues to survive and proliferate prodigiously. To
understand cancer, therefore, it is important to understand the normal
social controls on cell turnover that cancer perverts.
Stem Cells and Proliferating Precursor Cells Generate a
Continuous Supply of Terminally Differentiated Cells
Most of the specialized, differentiated cells that need continual replacement
are themselves unable to divide. This is true of red blood cells, the
epidermal cells in the upper layers of the skin, and the absorptive and
goblet cells of the gut epithelium. Such cells are referred to as terminally
differentiated: they lie at the dead end of their developmental pathway.
The cells that replace the terminally differentiated cells that are lost are
generated from a stock of proliferating precursor cells, which themselves
usually derive from a much smaller number of self-renewing stem cells.
Stem cells are not differentiated and can divide without limit (or at least
for the lifetime of the animal). When a stem cell divides, though, each
daughter has a choice: either it can remain a stem cell, or it can embark
on a course leading to terminal differentiation, usually via a series of
precursor-cell divisions (Figure 20–34). The job of the stem cells and precursor
cells, therefore, is not to carry out the specialized function of the
differentiated cells, but rather to produce cells that will.
Both stem cells and proliferating precursor cells are usually retained in
their resident tissue along with their differentiated progeny cells. Stem
cells are mostly present in small numbers and often have a nondescript
appearance, making them difficult to spot; in some tissues, specific
molecular markers can help identify them. Despite being undifferentiated,
stem cells and precursor cells are nonetheless developmentally
restricted: under normal conditions, they stably express sets of transcription
regulators that ensure that their differentiated progeny will be of the
appropriate cell types.
terminally
differentiated
cells
TERMINAL DIFFERENTIATION
Figure 20–34 When a stem cell divides, each daughter can either
remain a stem cell (self-renewal) or go on to become terminally
differentiated. The terminally differentiated cells usually develop
from proliferating precursor cells (sometimes called transit amplifying
cells) that divide a limited number of times before they terminally
differentiate. Stem-cell divisions can also produce two stem cells or two
precursor cells, as long as the pool of stem cells is maintained.