Molecular Mechanisms Regulating Spermatogonial Stem Cell Fate Decisions - Male Germline Stem Cells Developmental and Regenerative Potential - page 147

including SSCs via regulation of cell survival and preventing differentiation. In
cultured mouse SSCs NANOS2 expression is not effected by GDNF stimulation
(Oatley et al. 2006 ) and other extrinsic factors that may influence its expression have
not been described.

7.3.3.3 OCT3/4

OCT3/4, a homeobox transcription factor encoded by the Pou5f1 gene, is critical
for maintenance of embryonic stem cell pluripotency (Nichols et al. 1998 ; Niwa
et al. 2000 ). Also, OCT3/4 is expressed by PGCs in the embryonic gonad and sper-
matogonia of pre-pubertal mice (Pesce et al. 1998 ). Because of these features,
OCT3/4 has been considered a factor that is potentially essential for SSC function
in mice. However, global disruption of Oct3/4 expression causes embryonic lethality
(Nichols et al. 1998 ) and tissue-specific Oct3/4 disruption in PGCs induces apop-
tosis (Ohbo et al. 2003 ). Thus, these phenotypes present difficulty in studying the
role of OCT3/4 function in SSCs of postnatal mice. However, transfection of cul-
tured spermatogonia with an OCT3/4 shRNA vector reduced the colonizing ability
of SSCs upon transplantation into recipient testes compared to cells treated with a
control shRNA (Dann et al. 2008 ). These results suggest that OCT3/4 plays an
important role in SSC function; however, whether that role is in regulating self-
renewal, differentiation, or survival is undefined. Impairment of either these poten-
tial SSC fates caused by permanent reduction of OCT3/4 expression would inhibit
colonization upon transplantation. Additionally, disrupted homing ability of SSCs
to their cognate niche upon transplantation, an effect that is independent of self-
renewal, would also cause impaired reestablishment of spermatogenesis. Permanent
reduction of OCT3/4 expression by stable shRNA transduction compared to tran-
sient reduction by siRNA treatment could alter homing efficiency and this effect
cannot be eliminated as a cause of reduced SSC colonization following transplanta-
tion; thus, the actual function of OCT3/4 in SSC biology remains to be further
elucidated. Recently, studies by Wu et al. ( 2010 ) indicate that expression of OCT3/4
in cultured mouse SSCs is not needed for their maintenance or self-renewal in vitro .
These conflicting reports regarding the importance of OCT3/4 in SSC functions
await clarification with future experimentation.

7.3.3.4 PLZF

In mice, expression of the transcriptional repressor promyelocytic leukemia zinc
finger protein ( Plzf , also termed Zbtb16 ) is important for several development path-
ways. PLZF belongs to the BTB/POZ-domain family of transcription factors and
functions as a repressor at the level of chromatin remodeling (Hong et al. 1997 ;
Payne and Braun 2006 ). Initial studies of Plzf null mice revealed disrupted limb and
axial skeleton development via regulation of HOX and bone morphogenic protein
gene expression (Barna et al. 2000 ). In the germline of male mice PLZF expression