Page 273 - 20dynamics of cancer

258 CHAPTER 12

15
13
Transit
cells 11
9

7
Potential
stem cells
5

Stem cells
3

Paneth
cells 1

Figure 12.5 Schematic of a small intestine crypt of a mouse. The crypt has
about 15 cells from the epithelial surface at the top to the base, as numbered
along the right. In three dimensions, the cylindrical lining of the mouse small
intestine crypt has about 200–250 cells. Modified from Marshman et al. (2002).

Figure 12.6 shows the cell lineage hierarchy of the mouse small intes-
tine. The active stem cells divide to give rise to daughter cells. One-half
of the daughter cells must remain active stem cells to continue future
renewal. The other half of the daughters begins the transit pathway to
differentiation.
In the first few transit divisions, T 1 –T 3 , the cells retain the potential
to return to fully active stem cells in order to replace stem cells that
die or to contribute to tissue renewal after injury. Some of those early
transit lineage cells differentiate into Paneth cells and flow downward;
the others continue to flow upward, divide, and eventually differentiate
into the mature epithelial cells. Within a week or so, the daughters of
the stem cells have flowed to the surface and died, to be replaced by
the continual flow from below. Figure 12.7 gives a rough idea of the
three-dimensional crypt architecture.
Gastrointestinal stem cells remain difficult to identify unambiguously.
Through various indirect studies, Bach et al. (2000) conclude that each
mouse small intestine crypt has 4–6 active stem cells. Those stem cells