Primordial Germ Cells (PGCs) are unipotent
precursors of the gametes. PGCs can give rise to a type of pluripotent stem
cells in vitro that are called embryonic germ (EG) cells. PGCs can also acquire
such pluripotency in vivo and generate teratomas. Under specific culture
conditions, PGCs can be reprogrammed to embryonic germ cells which are capable
of expression of key pluripotency markers, such as Pou5f1(Oct4), Sox2 and
Nanog. One approach to derive EG cells is manipulation of intracellular
signaling pathways that play an important role in the pluripotency induction.
Wnt/β-catenin signaling pathway plays major roles in various cell processes
such as proliferation, differentiation, migration, survival, apoptosis and
pluripotency. For the induction of pluripotency and reprogramming of PGCs into
EG cells, Wnt/β-catenin signaling pathway should be activated and using small
molecules is one of the methods for reaching this objective. Glycogen synthase
kinase 3 (GSK3), is one of the important molecules of canonical pathway of
Wnt/β-catenin which signaling and inhibition of GSK3 by CHIR99021 small
molecule, causes the activation of this pathway but it is not sufficient for
reprogramming the PGCs into EG cells. In order to efficiently derive EG cells,
MAPK signaling pathway should be inhibited simultaneously with Wnt/β-catenin
signaling pathway, using small molecule PD0325901. Thus, the activation of the
Wnt/β-catenin signaling pathway and the simultaneous inhibition of the MAPK
pathway, can induce pluripotency in the rat PGCs and their reprogramming into
EG cells.
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