Page 277 - 20dynamics of cancer

262 CHAPTER 12

capacity for self-renewal and common cells that divide only a few times.
Those cycling cells with limited capacity for self-renewal are thought to
be the transit population (Watt 1998).
Figure 12.8 shows Potten’s model of the epidermal proliferation unit
for mice (Potten 1974, 1981; Potten and Booth 2002). Each approxi-
mately hexagonal unit of surface skin renews from a basal layer com-
prising about ten cells, of which only one basal stem cell renews the
unit.
Human skin is more complex: it has variable thickness in different lo-
cations, often has more layers than mouse skin, and has an undulating
basal layer. Most authors agree that stem cells reside at the basal layer
and give rise to an upward-migrating transit lineage. Controversy con-
tinues over the location of the stem cells in the basal layer, the frequency
of stem cells among basal cells, and the architecture of stem-transit lin-
eages and proliferative units (Potten and Booth 2002; Ghazizadeh and
Taichman 2005).
The hairs in the epidermis renew by a different process. Figure 12.9
shows the hair cycle, in which each follicle alternates between rest and
growth phases. During hair growth, there seems to be a stem-transit
type of architecture: stem-like cells replace themselves in the follicular
germ and simultaneously initiate transit lineages that move up and con-
tinue to divide. After the growth phase, the lower part of the follicle
regresses.
It remains unclear where the stem cells come from to reseed the fol-
licular germ at the start of the next growth phase. Those stem cells may
come from cells in the follicular germ of the rest phase, shown as FG(s?)
in Figure 12.9, or the next round of stem cells may migrate down from
daughter cells produced by the stem cells in the bulge region. Potten
and Booth (2002) emphasized the difficulty of interpreting various stud-
ies on this issue. Two recent studies favor the bulge stem cells as the
progenitors for each new round of follicular growth (Morris et al. 2004;
Kim et al. 2006).
In development, the stem cells of the bulge region appear to be the
ultimate source for the interfollicular stem cells (those, for example, in
Figure 12.8) and at least for the initial seeding of the follicular germ.
After injury, the bulge stem cells can regenerate the hair follicle, seba-
ceous gland, and interfollicular proliferative units (Cotsarelis et al. 1990;
Taylor et al. 2000; Potten and Booth 2002).