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

1220 Chapter 22: Stem Cells and Tissue Renewal
Stem cells are required wherever there is a recurring need to replace differentiated
cells that cannot themselves divide. Although a stem cell must be able
to divide, it does not necessarily have to divide rapidly; in fact, many stem cells
divide at a relatively slow rate.
Stem cells are of many types, specialized for the genesis of different classes
of terminally differentiated cells—intestinal stem cells for intestinal epithelium,
epidermal stem cells for epidermis, hematopoietic stem cells for blood, and so on.
Each stem-cell system nevertheless raises similar fundamental questions. What
are the distinguishing features of the stem cell in molecular terms? What conditions
serve to keep the stem cell in its proper place and to maintain its stem-cell
character? What decides whether a given daughter cell commits to differentiation
or remains a stem cell? In a tissue where several distinct types of differentiated
cells must be produced, are they all derived from a single type of stem cell, or is
there a distinct type of stem cell for each one?
SELF-RENEWAL
stem cell
Wnt Signaling Maintains the Gut Stem-Cell Compartment
For the gut, the beginnings of an answer to these questions came from studies of
cancer of the colon and rectum (the lower end of the gut, also known as the large
intestine). Some people have a hereditary predisposition to colorectal cancer and,
in advance of the invasive disease, develop large numbers of small precancerous
tumors (adenomas) in the lining of this part of the gut (Figure 22–4). The appearance
of these tumors suggests that they have arisen from intestinal crypt cells that
have failed to halt their proliferation in the normal way. As discussed in Chapter
20, the cause has been traced to mutations in the Apc (adenomatous polyposis
coli) gene: the tumors arise from cells that have lost both gene copies. Because
Apc codes for a protein that prevents inappropriate activation of the Wnt signaling
pathway (see Figure 15–60), this loss of Apc is presumed to mimic the effect of
continual exposure to a Wnt signal. The suggestion, therefore, is that Wnt signaling
normally keeps crypt cells in a proliferative state, and that a cessation of exposure
to Wnt signaling normally makes them stop dividing as they leave the crypt.
terminally
differentiated
cell
Figure 22–3 The definition of a stem cell.
Each daughter produced when a stem cell
divides can either remain a stem cell or
go on to become terminally differentiated.
In many cases, the daughter that opts for
terminal differentiation undergoes additional
cell divisions before terminal differentiation
is completed; such cells are called transit
amplifying cells.
MBoC6 m23.05/22.03
Stem Cells at the Crypt Base Are Multipotent, Giving Rise to the
Full Range of Differentiated Intestinal Cell Types
It has long been suspected that all the differentiated cell types in the lining of the
intestine derive from a single type of stem cell. But firm proof was lacking, and the
precise nature and location of the stem cells were disputed.
To solve the problem, and indeed to understand the organization of any stemcell
system, we need to discover how its cells are related to one another—who
NORMAL COLON
ADENOMA
200 µm
Figure 22–4 An adenoma in the human
colon, compared with normal tissue
from an adjacent region of the same
person’s colon. The specimen is from a
patient with an inherited mutation in one of
his two copies of the Apc gene. A mutation
in the other Apc gene copy, occurring in
a colon epithelial cell during adult life, has
given rise to a clone of cells that behave
as though the Wnt signaling pathway is
permanently activated. As a result, the
cells of this clone form an adenoma—an
enormous, steadily expanding mass of
giant cryptlike structures.