Pluripotent Stem Cells from the Postnatal Testis: Unlocking the Potential of Spermatogonial Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 28

Fig. 2.1 Expression of core pluripotency-associated genes OCT4, SOX2 , and NANOG in the
testis. Relative levels are denoted by black bars (high), gray bars (down-regulated but detectable),
and white bars (absent) for mouse and human testis in vivo . Boxes at right denote expression in
long-term SSC culture. This data represents a summary of findings from multiple studies
(Kanatsu-Shinohara et al. 2004, 2005b ; Pesce et al. 1998 ; Yoshimizu et al. 1999 ; Ohbo et al. 2003 ;
Ohmura et al. 2004 ; Tadokoro et al. 2002 ; Buaas et al. 2004 ; Tokuda et al. 2007 ; Looijenga et al.
2003 ; Rajpert-De et al. 2004 ; Seandel et al. 2007 ; Dann et al. 2008 ; Imamura et al. 2006 ; Avilion
et al. 2003 ; Western et al. 2005 ; Perrett et al. 2008 ; de Jong et al. 2008 ; Shi et al. 2006 ; Chambers
et al. 2003 ; Yamaguchi et al. 2005 ; Hoei-Hansen et al. 2005 ; Yeom et al. 1996 ) (see Addendum ).
Question marks indicate absence of published data
Oct4 gene fragment containing both the distal enhancer and the epiblast-specific
proximal enhancer, the investigators were unable to directly visualize GFP expression
more than 10 days after birth (Yoshimizu et al. 1999 ). Using similar Oct4/GFP
transgenic reporter mice, Ohbo et al. ( 2003 ) identified Oct4 -expressing sper-
matogonia (containing the majority of stem cell activity) in mice up to 14.5 days
postnatally, after which point expression decreased (Ohbo et al. 2003 ). A subsequent
study revealed Oct4 expression by RT-PCR in the Ep-CAM + fraction of adult Oct4/
GFP + cells (Ohmura et al. 2004 ). However, detection of endogenous Oct4 protein in
histologic sections of the adult testis required significant amplification in the latter
study, due to low levels of antigen compared to what was seen in the spermatogonia
of younger animals. Nonetheless, Tadokoro et al. ( 2002 ) confirmed Oct4 protein
expression in a substantial subpopulation of adult undifferentiated spermatogonia in
progeny-deficient strains of mice and proposed that Oct4 expression is reversible in
SSCs, depending on microenvironmental conditions, although the functional signifi-
cance of this result was not clear. Buaas et al. ( 2004 ) demonstrated co-expression of
Oct4 and Plzf, a marker of undifferentiated spermatogonia, in adult mouse testes,
while Tokuda et al. ( 2007 ) found co-expression of Oct4 and Cdh1 in adults (Buaas
et al. 2004 ; Tokuda et al. 2007 ). Taken together, these studies suggest that a subset
of murine spermatogonia maintain Oct4 expression into adulthood, albeit at relatively
low levels under normal (i.e., nonpathological) conditions.
In the human testis, though fewer data are available, OCT4 expression in the
male germline appears rapidly down regulated after ~20 weeks of gestation (Looijenga
et al. 2003 ; Rajpert-De et al. 2004 ). A small number of OCT4-positive cells are