Page 279 - 20dynamics of cancer

264 CHAPTER 12

OTHER TISSUES
The blood, intestine, and skin renew frequently and have clear stem-
transit architectures. Several other tissues also appear to have stem
lineages that may provide a source for regular renewal, a reservoir for
tissue repair, or daughter cell lineages that terminally differentiate (La-
jtha 1979; Watt 1998).
Mammalian spermatogenesis has a clearly defined stem-transit archi-
tecture of renewal and differentiation (de Rooij 1998). In other tissues,
the details of lineage history are less clear at present. Clarke et al. (2003)
discuss a model of breast epithelium renewed by a stem-transit hierar-
chy of differentiation. Numerous recent articles describe the properties
of breast stem cells (reviewed by Dontu et al. 2003; Liu et al. 2005; Vil-
ladsen 2005). Rizzo et al. (2005) discussed a stem-transit pathway of
renewal for the normal prostate, but at present we have only limited un-
derstanding of tissue architecture in the prostate. Cells with some stem-
like properties may occur in many tissues, but cell lineage architectures
probably vary according to demands for cell turnover and regeneration.

12.3 Symmetric versus Asymmetric Stem Cell Divisions

To maintain a pool of N stem cells in a niche, each stem division must
on average produce one daughter stem cell and one daughter that dif-
ferentiates. Regulation of stem cell numbers may occur either by sym-
metric or asymmetric stem cell division (Cairns 1975; Watt and Hogan
2000; Morrison and Kimble 2006).
In symmetric division, each replication produces two identical daugh-
ter cells. Random processes then determine whether 0, 1, or 2 of the
daughters remain stem cells while the other daughters differentiate.
Over the whole pool of N stem cells, some process must regulate the
probability of differentiation such that on average each stem division
gives rise to one stem and one differentiated daughter.
In asymmetric division, the daughters differ. One daughter remains as
a stem cell to replace the mother, and the other daughter differentiates.
The shape of cell lineages and the rate of evolutionary change in lin-
eages depend on whether stem cells divide symmetrically or asymmet-
rically. I discuss those lineage consequences in the next section. Here, I