Abstract
Wnt signaling has been implicated in promoting somatic cell reprogramming. However, its molecular mechanisms remain unknown. Here we report that Wnt/β-catenin enhances iPSCs induction at the early stage of reprogramming. The augmented reprogramming induced by β-catenin is not due to increased total cell population or activation of c-Myc. In addition, β-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/β-catenin signaling.
Highlights
Wnt signaling plays an important role in somatic cell reprogramming
-cateninϪ/Ϫ induced pluripotent stem cells (iPSCs) are indistinguishable from murine ESCs (mESCs) and -catenin iPSCs, based on cell morphology, Alkaline Phosphatase (AP) staining, and stage-specific embryonic antigen 1 (SSEA1) staining
We found that overexpression of -catenin stimulated iPSCs induction and such induction was partially inhibited by dominant negative TCF4 (DN-TCF4) expression (Fig. 2A)
Summary
Results: Through interaction with Klf, Oct and Sox2, -catenin enhances expression of pluripotency circuitry genes to promote somatic cell 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 Klf, Oct, and Sox, further enhancing expression of pluripotency circuitry genes. -catenin interacts with reprogramming factors Klf, Oct, and Sox, 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. A recent study demonstrated that -catenin was able to form a complex with Oct in a TCF-independent manner to enhance mESC pluripotency [12] These results indicate that -catenin seems to be important for self-renewal. -catenin has different roles in pluripotent stem cell self-renewal and reprogramming regulation
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