Stem Cell Niche System in Mouse Spermatogenesis - Male Germline Stem Cells Developmental and Regenerative Potential - page 166

system is advantageous in that it can detect the behaviors of the cells of interest
in the process of homeostasis, without disturbing the normal architecture and
functioning of the seminiferous tubules. Pulse-labeling of A undiff marked by the
expression of NGN3 (Yoshida et al. 2004 ) revealed that A undiff include both stem
and transit amplifying progenitor cells, the latter of which are defined by their
proliferation and differentiation without self-renewal. It is also shown that some
A undiff that are destined for differentiation in homeostasis do contribute to post-
transplantation colony-formation and postinsult regeneration (i.e., “potential
stem cells”) (Nakagawa et al. 2007 ; Yoshida et al. 2007a ). Therefore, it may be
difficult to provide a universal definition of “spermatogenic stem cells.” Although
the central role of A s can be acknowledged intuitively, it is also strongly sug-
gested that, within the A undiff population, varying sets of cells play active roles in
different aspects of stem cell functions (such as homeostasis versus regeneration/
colony formation) (Nakagawa et al. 2007 ; Yoshida et al. 2007a ). Recently, it has
also been suggested that some of the so-called differentiating spermatogonia may
retain the stem cell potential to form colonies after transplantation or in vitro
cultivation (Barroca et al. 2009 ).
The stem cell niche system in the mouse spermatogenesis may not be as simple
as that in Drosophila gonads. This issue needs to be further investigated carefully.

8.5 Niche Microenvironment in the Mouse Testis

Sertoli cells, peritubular myoid cells, and the basement membrane (components of
the basal compartment of seminiferous tubules, see Fig. 8.2f ) are often described to
comprise the mammalian spermatogenic stem cell niche (Ogawa et al. 2005 ; Hess
et al. 2006 ). This is correct but not a fully adequate description. This cannot explain
why only a limited number of spermatogonia are stem cells, prompting the notion
of the lack of uniformity over the basal compartment.
Given the seemingly uniform morphology of the seminiferous tubules, a
straightforward strategy for investigating the stem cell niche is to localize the can-
didate stem cell populations. Along this line of thought, a series of experiments
have been performed to address the localization of A undiff . Chiarini-Garcia and col-
leagues examined the localization of A undiff based on the observation of plastic-
embedded thin sections, and found that A undiff , within the basal compartment,
preferentially localized to the area adjacent to the interstitium, compared to attach-
ing to the neighboring tubules (Chiarini-Garcia et al. 2001, 2003 ). More recently,
the author's group has extended this finding by three-dimensional reconstitution
and an originally developed in vivo live imaging system that allows one to trace the
live behaviors of A undiff without disturbing the normal architecture (Yoshida et al.
2007b ). As shown in Fig. 8.4 , A undiff preferentially localized to the area adjacent to
interstitial spaces, namely to the blood vessels with medium thickness (i.e., arterioles
and venules). It is noteworthy that these testicular vessels accompany the Leydig
cells and other interstitial cells (Hinton and Turner 1993 ). Interestingly, A undiff