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. Mouse embryonic fibroblasts (MEFs) introduced with 6 different combinations of TFs with triplicates

我们在此报道：将Zic家族（Zic1/2/3）与孤核受体家族（Esrrb、Nr5a2）的转录因子（Transcription Factors, TFs）与Oct4、Sox2及Klf4（以下简称OSK）共同转导至小鼠成纤维细胞时，可协同提升细胞重编程效率。为阐明该协同效应的分子机制，我们对引入重编程因子6天后的全局基因表达谱进行了分析。结果显示，当单独将上述任一转录因子与OSK共转导时，其核心靶基因存在差异，但包括Dppa2等多能性标志物在内的相当比例基因呈现协同上调趋势。进一步分析表明，代谢通路是上述转录因子实现高效重编程的关键靶标。本研究使用了6种不同转录因子组合转导的小鼠胚胎成纤维细胞（Mouse Embryonic Fibroblasts, MEFs），每组均设置三次生物学重复。