Making Germ Cells from Human Embryonic Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 65

Fig. 3.4 Diagrammatic representation of the different stages of human germ cell development
during human ES cell differentiation resolved from both in vivo and in vitro studies. Shown are
the expression patterns of genes that define undifferentiated ES cells and each subsequent stage of
germ cell development with each gene name on the left and its temporal expression indicated by
the arrows extending to the right . All of the genes are enriched in germ cells relative to somatic
cells, and those that are only expressed in the germ cells following the blastocyst stage embryo
in vivo are indicated by an asterisk . Note that Gdf9 is an adult oocyte-specific marker in mouse,
and TEKT1 is an adult spermatid-specific marker in human and mouse
those that were germ cell-specific (not expressed in somatic lineages), and those
that were germ cell-enriched (highly expressed in germ cells with limited expres-
sion in somatic cells). The genes GDF3 and NANOG were expressed in undifferen-
tiated ES cells. Surprisingly however, as depicted in Fig. 3.4 , undifferentiated
human ES cell colonies also expressed RNA and protein for the germ cell-specific
genes DAZL and STELLAR , as well as the germ cell-enriched genes cKIT (a marker
of premeiotic migrating germ cells and pre-meiotic germ cells of the postnatal
testis), and NANOS1 , PUM1 , and PUM2 (markers specific to premeiotic primordial
germ cells of the fetal gonads) (Clark et al. 2004a ).
The presence of this early germ cell program in undifferentiated hESCs indi-
cates that either: hESCs originate from PGC precursors in the inner cell mass;
hESCs and PGCs share common genetic programs of pluripotency, self-renewal,
and survival; and/or that a subpopulation of hESCs spontaneously differentiates
into the germ cell lineage. In support of the hypothesis that hESCs in vitro and the
inner cell mass in vivo are not identical cell populations it was discovered that the
transcriptional profiles of these cell types were different. Cells of the inner cell