Regulation of Induced Pluripotent Stem ( iPS) Cell Induction by Wnt/β-Catenin Signaling

Background: Wnt signaling plays an important role in somatic cell reprogramming. Results: Through interaction with Klf4, Oct4 and Sox2, -catenin enhances expression of pluripotency circuitry genes to promote somatic cell reprogramming. However, -catenin is not required for pluripotent stem cell self-renewal. Conclusion: Wnt/-catenin signaling has different roles in pluripotent stem cell self-renewal and somatic cell reprogramming. Significance: These studies reveal novel mechanisms underlying the reprogramming process by Wnt/-catenin signaling. Wnt signaling has been implicated in promoting somatic cell reprogramming. However, its molecular mechanisms remain unknown. Here we report that Wnt/-catenin enhances iPSCs induction at the early stage of reprogramming. The augmented reprogramming induced by -catenin is not due to increased total cell population or activation of c-Myc. In addition, -catenin interacts with reprogramming factors Klf4, Oct4, and Sox2, further enhancing expression of pluripotency circuitry genes. These studies reveal novel mechanisms underlying the regulation of reprogramming somatic cells to pluripotency by Wnt/-catenin signaling.