Primordial Germ-Cell Development and Epigenetic Reprogramming in Mammals - Current Topics in Developmental Biology - page 157

This marked difference in pig PGC specification is of great interest and
merits further investigation in other organisms. It will also be interesting
to measure the expression of other pluripotency genes in the porcine
germline to ascertain whether this early expression pattern is unique to
Nanog . Oct4 expression has been demonstrated in rat PGCs at E10
( Leitch et al., 2010 ) and in rat genital ridges ( Northrup et al., 2011 ). Notably,
rat genital ridges also appear to express Klf4 ( Northrup et al., 2011 ).
Although specific expression in PGCs has not been demonstrated, this
may well represent a significant difference with mouse PGCs in which
Klf4 is not expressed ( Durcova-Hills et al., 2008 ). The pluripotency-
associated cell-surface marker SSEA-1 seems to be a well-conserved marker
of PGCs in a range of species including mouse ( Fox, Damjanov, Martinez-
Hernandez, Knowles, & Solter, 1981 ), pig ( Takagi et al., 1997 ), sheep
( Ledda et al., 2010 ), goats ( K ¨ hholzer et al., 2000 ), and humans (see below),
but not in the rat ( Encinas, Zogbi, & Stumpp, 2012 ).
Human PGCs/gonocytes express pluripotency markers, including OCT4,
NANOG, c-KIT, SSEA-1, and SSEA-4 ( Gaskell, Esnal, Robinson, Anderson,
& Saunders, 2004; Kerr, Hill, Blumenthal, & Gearhart, 2008a, 2008b ). How-
ever, the pluripotency-associated transcription factor SOX2 is absent in human
PGCs ( Perrettetal.,2008 ). SOX2 has been shown to cooperatewithOCT4 and
NANOG to regulate pluripotency in both human and mouse ES cells ( Boyer
et al., 2005; Fong, Hohenstein, & Donovan, 2008; Wang et al., 2006 ), and is
expressedinmouseinnercellmass(ICM)andPGCs( Avilion et al., 2003 ), as
well as in human ICM ( Cauffman,DeRycke,Sermon,Liebaers,&Vande
Velde, 2009 ). Interestingly, Sox2 expression appears to be downregulated
during sheep PGC development, despite the maintenance of Oct4 and
Nanog ( Ledda et al., 2010 ). Studies in a range of othermammalswill help to ascer-
tain whether low or absent Sox2 expression in PGCs is a more general feature.
In mouse PGCs, most of the specification- and pluripotency-associated
genes are downregulated before the onset of sex-specific differentiation.
However, in human, these genes, including BLIMP1, PRMT5, TCFAP2C,
LIN28, OCT4, and NANOG, are still expressed in a portion of germ cells at
the second or even the third trimester ( Childs et al., 2012; Eckert et al., 2008;
Gillis et al., 2011; Kerr et al., 2008a, 2008b; Pauls et al., 2005 ). In particular,
a PGC-like population of OCT4

cells can still be
observed in the human fetal ovary at week 13 postconception, 3 weeks after
the onset of meiosis in some female germ cells ( Kerr et al., 2008a ). However,
these OCT

þ /NANOG þ /c-KIT þ

germ cells do not coexpress the meiosis marker
SYCP3 ( Childs et al., 2012 ). This suggests that a subpopulation of germ cells

þ /LIN28 þ