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

1246 Chapter 22: Stem Cells and Tissue Renewal
committed
progenitor cell
stem cell
CONTROLLABLE PARAMETER
1. Frequency of stem-cell division
2. Probability of stem-cell death
3. Probability that stem-cell daughter
will become a committed progenitor
cell of the given type
Figure 22–34 Some of the parameters
through which the production of
blood cells of a specific type might
be regulated. Studies in culture suggest
that various colony-stimulating factors
(CSFs) can affect all of these aspects of
hematopoiesis.
4. Division cycle time of committed
progenitor cell
5. Probability of progenitor-cell death
6. Number of committed progenitorcell
divisions before terminal
differentiation
7. Lifetime of differentiated cells
terminally
differentiated
blood cell
macrophage CSF, can exert all these effects, although it is still not clear which are
most important in vivo.
Studies in vitro indicate, moreover, that there is a large element of chance in
the way a hematopoietic cell behaves—a reflection, presumably, of “noise” in the
genetic control system, as discussed in Chapters 7 and 8. If two sister cells are
taken immediately after a cell division and cultured apart under identical conditions,
they frequently give rise to colonies that contain different types of blood
cells or the same types of blood cells in different numbers. Thus, both the programming
of cell division and the process MBoC6 m23.46/22.34
of commitment to a particular path of
differentiation seem to involve random events at the level of the individual cell,
even though the behavior of the multicellular system as a whole is regulated in a
reliable way. The sequence of cell fate restrictions shown earlier, in Figure 22–31,
conveys the impression of a program executed with computer-like logic and precision.
Individual cells may be more varied, quirky, and erratic, and may sometimes
progress by other decision pathways from the stem-cell state toward terminal
differentiation.
Regulation of Cell Survival Is as Important as Regulation of Cell
Proliferation
The default behavior of hematopoietic cells in the absence of CSFs is death by
apoptosis (discussed in Chapter 18), and the control of cell survival plays a central
part in regulating the numbers of blood cells. The amount of apoptosis in the
vertebrate hematopoietic system is enormous: billions of neutrophils die in this
way each day in an adult human, for example. In fact, most neutrophils produced
in the bone marrow die there without ever functioning. This futile cycle of production
and destruction presumably serves to maintain a reserve supply of cells
that can be promptly mobilized to fight infection whenever it flares up, or phagocytosed
and digested for recycling when all is quiet. Compared with the life of the
organism, the lives of cells are cheap.
Too little cell death can be as dangerous to the health of a multicellular organism
as too much proliferation. As noted in Chapter 18, mutations that inhibit cell
death by causing excessive production of the intracellular apoptosis inhibitor