Page 274 - 20dynamics of cancer

STEM CELLS: TISSUE RENEWAL 259

Mature enterocytes, goblet cells

T 6

Dividing
T 5 transit cells

T 4
Commitment to
differentiation
T 3
Potential
T 2 clonogenic
stem cells
T 1

S Actual steady state Paneth
stem cells cells

Figure 12.6 Cell lineage hierarchy in a small intestine crypt of a mouse. Ac-
tive stem cells give rise to daughter stem cells that remain near the base of the
crypt and the first generation of the transit lineage pathway (T 1 ), the potential
clonogenic stem cells. The early transit generations retain the ability to return
to fully active stem cells, but normally they move either up or down the crypt.
If the cells move down, they differentiate into Paneth cells that line the base of
the crypt. If the cells move up, they differentiate into goblet cells and then ma-
ture enterocytes, after which they die and are shed from the epithelial surface.
Redrawn from Marshman et al. (2002).

divide about once per day; each crypt produces about 300 new cells per
day. There are about six transit divisions, so it takes about one week
for a daughter cell of the stem lineage to move up, differentiate, and die
5
at the surface. The mouse small intestine has about 7 × 10 crypts, so
8
the whole small intestine of the mouse produces about 2 × 10 cells per
day.
The large intestine (colon) has a similar architecture but lacks Paneth
cells. Cancer occurs more often in the large intestine than in the small in-
testine, in spite of the similar tissue architecture and pattern of cellular
renewal. Probably the colon suffers greater concentrations of carcino-
gens that result from digestion and excretion. The human large intestine
7
has around 10 crypts that each renew about once per week. If a stem
lineage in the human colon divided once every six days for 80 years, it