Gene expression analysis of mouse embryonic fibroblasts reprogrammed with OSK, Esrrb and Zic3

We report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.

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Sone M, Morone N, Nakamura T, Tanaka A, Okita K, Woltjen K, Nakagawa M, Heuser JE, Yamada Y, Yamanaka S, Yamamoto T