Pathways to Pluripotency: How Germ Cells Make Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 8

Fig. 1.2 Cartoon depicting primordial germ cell migration into the developing gonad and
subsequent differentiation into gonocytes. Upper panel shows the major features of the embryo
and the region depicted in detail in the lower figure . ( a ) Shows the position of PGCs ( red circles )
in the 6.5 dpc embryo. By 8.5 dpc ( b ), the embryo has enlarged, the anterior posterior axis ( A ↔ P )
is well defined and the germ cells begin to migrate into the embryo proper ( arrowed ) from their
location near the allantois. The dotted line in ( b ) represents the area of section shown in ( c ). By
the next day of development ( c ) the germ cells are found in the hindgut. Lower panel depicts sec-
tions through embryos at 9.5, 10.5, 12.5, and 15.5 dpc. At 9.5 dpc PGCs (depicted by the red dots )
are localized within the hindgut, which is slung in the coelomic cavity suspended by both a dorsal
and ventral mesentery. By the next day of development (10.5 dpc) the ventral mesentery has
regressed and the PGCs have begun to migrate up the dorsal mesentery towards a thickened area
of the dorsal body wall, the genital ridge or gonad anlagen, which is the structure that will form
the gonad. Within the next two days of development, all of the PGCs will have reached the devel-
oping gonad. Once they have reached the gonad they will differentiate into gonocytes ( green cir-
cles ). In males at 15.5 dpc, the gonocytes will become incorporated into the developing testis
cords. In animals that are susceptible to teratomas formation such as Ter/+ animals, small nests of
proliferating cells ( red circles ) are seen within the developing gonad. These cells, termed embryo-
nal carcinoma cells, retain the markers of PGCs such as TNAP and SSEA-1 and are also shared
with other pluripotent stem cells
Teratomas are bizarre tumors that contain cell types representative of cells derived
from all three primary germ layers present in the embryo. Because of their origin
from germ cells these tumors may also be referred to as testicular germ cell tumors
(TGCTs). Although teratomas can arise in female gonads their mechanism of
development is different and quite distinct from those of TGCTs.
Importantly, studies of EC cells demonstrate that they can give rise to all the cell
types present in the teratoma and, therefore, they could be defined as pluripotent.
In defining EC cells as pluripotent Stevens compared them to the pluripotent cells
of the early embryo. It was only later that it was discovered that the pluripotent cells of