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STEM CELLS: TISSUE RENEWAL 255

(a)

(b)

Figure 12.2 Alternative stem-transit designs to renew a tissue based on asym-
metric stem cell division. Each pattern begins with a single stem cell at the
lower left. Time moves to the right, as the stem lineage progresses along the
lower row in each case. Stem cells divide asymmetrically in these two patterns,
each stem cell division producing one daughter transit cell and one daughter
stem cell. All cells that remain in the tissue over time trace their ancestry back
through a linear history of stem cell divisions. Derived from Cairns (1975).

the tissue over time. Those 16 stem cell divisions also trace a linear
history of descent, so that the final stem cell on the bottom right traces
its ancestry back through the lineage that forms the bottom row. Any
mutations that remain in the tissue over time must occur in the stem
cell lineage.
Figure 12.2b presents a second pattern by which the stem lineage may
produce 16 transit cells. The original stem cell at the bottom left divides
to produce one new daughter cell to the right and one new transit cell
to the top. The transit cell then goes through two further rounds of cell
division, producing four transit cells to renew the tissue for each stem
cell division. In this case, the tissue produces 16 transit cells with just
four rounds of stem cell division. Again, any mutations that remain in
the tissue over time must occur in the stem cell lineage, but with just
four stem cell divisions in (b), that pattern reduces the accumulation of
mutations relative to the pattern in (a) with 16 stem cell divisions.
Those tissues that renew most often appear to have a stem-transit
architecture, following the pattern in Figure 12.2b.

HEMATOPOIETIC RENEWAL
The numerous distinct blood cell types derive from hematopoietic
stem cells via a complex transit hierarchy (Weissman 2000; Kondo et al.