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CELL LINEAGE HISTORY 293

H H
E E
E(s) E(s) E(s)
SG
SG
B(s) Hair B(s)
FG(s?) cycle
DP

Resting (telogen) phase
DP
FG(s)

Growing (anagen) phase

E Epidermis B Bulge
H Hair SG Sebaceous gland
DP Dermal papilla (s) Stem cells
FG Follicle germ

Figure 14.2 Life cycle of a mammalian hair follicle. As the follicle moves from
the rest phase to the growth phase, the follicular germ region moves downward
and becomes an active site of cell division. Transit cells from the follicular germ
move upward to form the growing hair. After a growth phase, the follicular germ
region regresses to reform the rest phase morphology. From Potten and Booth
(2002).

cells in the bulge region. That cycle would create a hierarchy of stem-
transit lineages: bulge stem cells divide to start the cycle; daughters
of the bulge cells form the follicular germ stem cells to feed the transit
lineages for hair growth; the follicular germ stem cells die and the follicle
regresses to resting morphology; the bulge cells divide again to start a
new cycle. In this cycle, only the rarely dividing bulge lineage remains
over time. Some evidence favors this stem cell hierarchy (Morris et al.
2004), but interpretation of the evidence remains ambiguous (Potten and
Booth 2002).
Kim et al. (2006) analyzed methylation patterns of human hair folli-
cles to evaluate the lineage history. Methylation patterns do not allow
one directly to reconstruct the lineage history. Instead, one uses the fact
that the frequency of methylated CpG nucleotide sites tends to increase
with mitotic age—the number of cellular generations back to the zygote
(Issa 2000; Yatabe et al. 2001). The actual methylation frequency in each