The Role of Wnt/β-catenin Signaling Pathway in Rat Primordial Germ Cells Reprogramming and Induction into Pluripotent State

 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.