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Tang, Doody, Tooze, & Surani, 2008
), all the major nodes in the pluripotency
network become reexpressed during PGC specification (
Chen et al., 2008;
Niwa, 2007
).
The transcriptome of
Blimp1
null PGCs indicates that a minority of
specification-associated genes are still induced in the absence of
Blimp1
,
suggesting that there are Blimp1-independent mechanisms during specifica-
tion (
Kurimoto et al., 2008
). However, in the absence of
Blimp1
, there is
almost complete failure to repress somatic differentiation genes, of which
over 70% remain expressed at levels comparable to somatic neighbors. Thus,
the initial speculation that Blimp1's primary role is the suppression of the
somatic mesodermal program is supported by transcriptome analysis
(
Kurimoto et al., 2008; Ohinata et al., 2005
).
Lin28 has been reported to function upstream of Blimp1 during PGC
specification (
West et al., 2009
).
Lin28
knockdown in ES cells reduces their
contribution to PGCs in chimeric mice, while overexpression increases
contribution (
West et al., 2009
). Blimp1 has been reported to be post-
transcriptionally regulated by let-7 miRNA targeting of its 3
0
-untranslated
region (UTR;
Nie et al., 2008
). The authors propose that Lin28 acts to
inhibit let-7-mediated suppression of Blimp1. Consistent with this, over-
expression of Blimp1 lacking its 3
0
-UTR can rescue the contribution of
Lin28
knockdown ES cells to PGCs (
West et al., 2009
). However, recently
Lin28
has been knocked out and the phenotype is more consistent with a
role in regulating germ cell proliferation rather than in PGC specification
(
Shinoda et al., 2013
)
Only two further genes with an early PGC phenotype have been
reported. Prdm14, like Blimp1, is a PR/SET domain containing protein
which had previously been reported to play a role in suppressing differen-
tiation markers in human ES cells (
Tsuneyoshi et al., 2008
).
Prdm14
knock-
out mice are sterile and show a progressive loss of PGCs commencing
around E7.5 and continuing until E12.5, although a few AP-positive cells
do remain even at this latter time point (
Yamaji et al., 2008
). The authors
examined single-cell cDNA libraries from E7.5 PGCs and found that
Prdm14
null PGCs had specifically failed to upregulate Sox2 and had
reduced levels of Stella. Differentiation markers were appropriately
repressed leading the authors to conclude that Prdm14, in contrast to
Blimp1, does not function to repress the somatic program but is required
for reacquisition of potential pluripotency. However, notably the
pluripotency genes
Nanog
and
Oct4
, and the PGC genes
Dnd1
and
Nanos3
were not affected by loss of
Prmd14
at this stage. Yamaji and colleagues also
