Pramef12 enhances reprogramming into na?ve iPS cells

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by forced expression of the transcription factors Oct3/4, Klf4, Sox2, and c-Myc (OKSM). Somatic cell nuclear transfer can also be utilized to reprogram somatic cells into totipotent embryos, suggesting that factors present in oocytes potentially enhance the efficiency of iPS cell generation. Here, we showed that preferentially expressed antigen of melanoma family member 12 (Pramef12), which is highly expressed in oocytes, enhances the generation of iPS cells from mouse fibroblasts. Overexpression of Pramef12 during the early phase of OKSM-induced reprogramming enhanced the efficiency of iPS cell derivation. In addition, overexpression of Pramef12 also enhanced expression of naive pluripotency-associated genes, Gtl2 located within the Dlk1-Dio3 imprinted region essential for full pluripotency, glycolysis-associated genes, and oxidative phosphorylation-associated genes, and it promoted mesenchymal-toepithelial transition during iPS cell generation. Furthermore, Pramef12 greatly activated beta-catenin during iPS cell generation. These observations suggested that Pramef12 enhances OKSM-induced reprogramming via activation of the Wnt/beta-catenin pathway.

Automated summary

This study found that Pramef12, highly expressed in oocytes, enhances the efficiency of reprogramming somatic cells into induced pluripotent stem cells (iPS cells) in mice. Pramef12 overexpression during the early phase of reprogramming also promotes the expression of pluripotency-associated genes, metabolic genes, and facilitates the transition of mesenchymal-to-epithelial during iPS cell generation. Furthermore, Pramef12 activates the Wnt/beta-catenin pathway, thereby enhancing OKSM-induced reprogramming.