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et al., 2008
).
Blimp1
expression is first detected in approximately six cells in
the prestreak E6.25 epiblast (
Ohinata et al., 2005
). Lineage tracing using a
Blimp1-
cre transgenic mouse indicates that Blimp1-positive cells in the epi-
blast are germline lineage-restricted. This apparently contradicts previous
lineage tracing experiments that found no lineage-restricted PGCs at E6.5
(
Lawson & Hage, 1994
). However, the small number of Blimp1-positive
cells at E6.5 makes it possible that these escaped labeling in the earlier exper-
iments, explaining why Lawson failed to find any lineage-restricted cells at
this stage. If recruitment to the germ-cell lineage is still occurring at E6.5,
then labeled Blimp1-negative cells may still divide to give a Blimp1-positive,
lineage-restricted PGC and a somatic sister cell (
McLaren & Lawson, 2005
).
PGC induction at E6.5 is still possible in the context of heterotrophic trans-
plants (
Tam & Zhou, 1996
) suggesting that ongoing recruitment to the lin-
eage is indeed feasible.
A global gene expression profiling study during the process of PGC spec-
ification, from E6.25 until E8.25, has provided an invaluable resource
(
Kurimoto et al., 2008
). The authors also included
Blimp1
null PGC-like
cells from two different developmental stages, allowing them to expand
on the previous characterization of these cells. In total, 134 single cells were
analyzed by microarray. This constitutes a huge data set but some important
patterns are particularly noteworthy. A significant developmental switch
appears to occur at the late-streak/no-bud stage (E6.75-E7.0) when
Blimp1-positive, HoxB1-positive cells become HoxB1-negative. Follow-
ing principal component analysis, Blimp1-positive, HoxB1-positive cells
segregate with somatic mesodermal cells across the first principal component
(PC1), whereas Blimp1-positive, HoxB1 negative cells cluster closely with
all later stages of PGC development. As PC1 accounts for the greatest degree
of variability in the transcriptome data, it suggests that this switch correlates
with a global gene expression change that represents the definitive specifi-
cation of PGCs.
Genes upregulated during the transition from a Blimp1-positive, HoxB1-
positive to Blimp1-positive, HoxB1-negative state include pluripotency-
associated genes
Nanog
,
Sox2
,
Klf2
,and
Stella
. Indeed, the expression
of pluripotency genes in PGCs has been noted before. For instance, Oct4
is expressed throughout PGC development (
Sch¨ ler, Dressler, Balling,
Rohdewohld, & Gruss, 1990; Yeom et al., 1996
), while Nanog protein
can be detected from E7.75 (
Yamaguchi, Kimura, Tada, Nakatsuji, &
Tada, 2005
) and Sox2 and Stella protein at E7.5 (
Kurimoto et al., 2008;
Saitou et al., 2002
). Thus, with the exception of Klf4 (
Durcova-Hills,
