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Fig. 8.3
Steps of the spermatogenic differentiation in mice. The mouse spermatogenic process is
divided into the stage of spermatogonia (mitotic cells), spermatocytes (meiotic cells), and sperma-
tids (haploid cells). The singly isolated spermatogonia are considered to be the most primitive
cells. The subsequent mitotic and meiotic divisions accompany incomplete cytokinesis to form
syncytia of 2
n
cells as indicated. See text for details
32 cells (A
aligned
or A
al
spermatogonia) (Russell et al.
1990
; de Rooij and Russell
2000
) (see Fig.
8.3
). Upon differentiation of A
undiff
to more advanced “differentiat-
ing spermatogonia,” the expression of c-Kit is highly up-regulated from essentially
no expression (Schrans-Stassen et al.
1999
). Transplantation assay demonstrated
that the c-Kit negative (~A
undiff
) population exhibited most of the colony-forming
activity (Shinohara et al.
2000
; Ohbo et al.
2003
), while investigations for the nar-
rower fractions have not been achieved.
The use of the posttransplantation colony formation as an assay for the stem cell
detection was essential for the establishment of long-term culture of the spermatogo-
nia with stem cell activity (Kanatsu-Shinohara et al.
2003
; Kubota et al.
2004
).
This success is also owed to the discovery of the important roles of GDNF (glial cell
line-derived neurotrophic factor) signaling, which was obtained from the loss-of-
stem-cell-maintenance phenotype observed in the mutants (Meng et al.
2000
). It can be
said that the
in vitro
culture system mimics some, although not the entire, essential
aspects of the
in vivo
stem cell niche system. Further, the stem cell behavior in
response to these signals can be assessed using the
in vitro
system (Yeh et al.
2007
).
A different approach for the functional identification of the stem cells was the
in vivo
pulse-chase strategy (Nakagawa et al.
2007
; Yoshida et al.
2007a
). This
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