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STEM CELLS: TISSUE RENEWAL 265

briefly review evidence with regard to whether stem divisions are sym-
metric or asymmetric.
Several recent studies support the asymmetric pattern of stem cell
division. Lechler and Fuchs (2005) showed in mice that dividing cells
at the basal layer of the epidermis produce asymmetric daughters: one
daughter moves upward while differentiating into a cell with limited
proliferative capacity, whereas the other undifferentiated daughter re-
mains at the basal layer and retains proliferative capacity. Asymmetric
division of stem cells appears to split daughters between the stem and
transit pathways. Asymmetry of daughter cell fate arises from asym-
metry in the orientation of the mitotic spindles: one daughter moves
upward from the basal membrane, and the other daughter remains near
the basement membrane where it receives signals to maintain stem char-
acteristics.
Drosophila spermatogenesis also divides its stem cells asymmetrically
by mitotic spindle orientation and signals in the basal stem niche (Ya-
mashita et al. 2003). It remains unclear whether mammalian sperm stem
cells divide symmetrically or asymmetrically.
Preliminary in vitro evidence suggests that mammalian hematopoietic
stem cells divide asymmetrically (Takano et al. 2004; Giebel et al. 2006);
however, this hypothesis of hematopoietic stem cell asymmetry requires
further analysis.
Although asymmetry seems to occur in a few particular cases, ob-
taining direct evidence of asymmetry remains technically challenging
(e.g., Giebel et al. 2006). Another line of evidence in favor of asymmetry
comes from the pattern by which DNA segregates to daughter cells.

12.4 Asymmetric Mitoses and
the Stem Line Mutation Rate
Cairns (1975) emphasized that in a stem-transit architecture, only the
stem lineage survives over time. Thus, only those mutations in the “im-
mortal” stem lineage remain in the tissue. Cairns argued that organisms
may use various mechanisms to reduce the mutation rate in the stem
lineage.