Wnt Signaling in Stem Cells and Cancer

Abstract

Mammalian development starts from a fertilized egg that initially generates few pluripotent cells which eventually give rise to the embryo proper. Different ‘flavors’ of pluripotency have been captured in vitro which led to the establishment of different pluripotent cell lines. Mouse embryonic stem cells (mESCs) are derived from the preimplantation embryo and have three defining properties: self-renewal, pluripotency, and contribution to chimera formation. By applying specific culture conditions or ectopic expression of the pluripotency factors, similar pluripotent cells can be derived from germ cells or differentiated cells referred to as embryonic germ (EG) and induced pluripotent cells (iPSCs), respectively. When established from post-implantation embryo, the cultured cells are termed epi stem cells (EpiSCs). EpiSCs have limited potential for chimerism and germ line transmission and require different culture conditions when compared to ESCs. Hence, mouse ESCs and EpiSCs represent two different phases of pluripotency usually referred to as the naïve and primed states. By employing genetic manipulation or specific culture conditions, the different pluripotent cells can be interconverted which leads to several intermediate states. Unlike their murine counterparts, human ESCs closely resemble the rodent primed EpiSCs and respond to similar signaling pathways. Tumorigenic transformation of primordial germ cells (PGC) and gonocytes can also give rise to pluripotent cells known as embryonal carcinoma cells (hECs), thought to represent the malignant counterpart of hESCs. Among different signaling pathways, Wnt signaling plays a central role in self-renewal and differentiation of pluripotent cells.