Increased efficiency in the generation of induced pluripotent stem cells by F bxw7 ablation

Induced pluripotent stem cells ( iPSC s) share many biological properties with embryonic stem cells ( ESC s), and are generated from somatic cells by expression of some transcription factors such as O ct3/4, S ox2, K lf4 and c‐ M yc. Among these factors, the abundance of c‐Myc is strictly regulated by Fbxw7, a subunit of S kp1‐ C ul1‐ F ‐box protein‐type ubiquitin ligase. We have now shown that the expression of F bxw7 was increased as ESC s differentiated. To investigate the role of F bxw7 in the ESC s/ iPSC s, we examined the impact of F bxw7 ablation in the efficiency in iPSC generation. The frequency of iPSC generation from mouse embryonic fibroblasts ( MEF s) lacking F bxw7 was markedly greater than that from control MEF s. Depletion of F bxw7 also resulted in promotion of iPSC generation. Morphology of iPSC clonies from F bxw7‐depleted MEFs appeared more undifferentiated than that from MEF s overexpressing c‐ M yc. Additional depletion of c‐ M yc did not abrogate the effect of F bxw7 depletion, suggesting that c‐ M yc accumulation is not necessarily required for the increased efficiency in iPSC generation by F bxw7 ablation. Substrates of F bxw7 other than c‐ M yc might therefore play a key role in iPSC generation. These results suggest that transient inhibition of Fbxw7 would be a more promising approach to efficient generation of i PSC s than c‐ M yc over‐expression.