Page 298 - 20dynamics of cancer

STEM CELLS: POPULATION GENETICS 283

Figure 13.6 Stem-transit design to renew a tissue based on symmetric stem
cell division and regulation of the stem pool to a constant size. Each alternative
begins with two stem cells at the left. The two stem cells differ genetically. Each
stem cell divides to produce two daughter cells; the solid versus dashed arrows
represent the distinct daughter cells. The arrows up or down lead to transit
cells; the arrows to the right lead to the replacement stem cells that remain at
the base of tissue for subsequent renewal. There are six distinct patterns. The
four patterns at the left retain genetic polymorphism in the stem pool and differ
only in the four ways in which the distinct daughter cells can be assigned to stem
or transit lineages. The two patterns at the right lose genetic variability in the
stem pool; each of those patterns can happen in only one way, because the two
daughters from each initial stem cell both move into the same compartment,
either stem or transit, and so allow only one possible arrangement of daughter
cells. Thus, with random choice of which cells remain in the stem pool, 4/6 of
the time the polymorphism in the stem pool with be retained, 1/6 of the time
the pool will become fixed for one genotype, and 1/6 of the time the pool will
become fixed for the other genotype.

lines, then natural selection favors short transit lineages and long stem
lineages.

13.3 Symmetric versus Asymmetric Mitoses

Suppose a tissue compartment, such as an intestinal crypt, maintains
N stem cells. To maintain a constant stem pool size, each stem cell
may divide asymmetrically, every division giving rise to one daughter
stem cell and one daughter transit cell. Alternatively, each stem cell
may divide symmetrically, giving rise to two daughters that retain the
potential to continue in the stem lineage; random selection among the
pool of excess potential stem cells reduces the stem pool back to N.