Investigation of molecular indicators related to the degree of pluripotency of iPS cells

虽然已经用各种方法产生了iPS细胞，但观察到了相当大的质量差异。本研究旨在寻找区分IPSCs质量的分子指标。我们重点研究了组蛋白-表观遗传修饰，并获得了以下结果。(1)组蛋白乙酰化加速仅见于具有高发育潜能的IPSCs。(2)低多能的IPSCs经TSA处理后，组蛋白乙酰化暂时积聚，从而提高其发育能力。(3)组蛋白修饰相关因子的表达分析表明，组蛋白乙酰化程度与c-Myc和某些HDAC的表达水平密切相关。在ES细胞中没有观察到如此密切的相关性。基因敲除实验表明，HDAC可能影响IPSCs的分化状态。(4)各IPSC的基因组完整性不是其发育潜力的直接原因。

Although iPS cells have been generated by various methods, considerable quality variation has been observed. This study aimed at finding the molecular indicators for discriminating the quality of iPSCs. We focused on the histone-epigenetic modifications, and obtained the following results. (1) Acceleration of the histone acetylation was observed only in iPSCs with high developmental potential. (2) TSA-treatment on iPSCs showing low pluripotency elicited a temporary accumulation of histone acetylation, resulting in improving their developmental ability. (3) Analysis of the expression of histone modification-related factors suggested a close correlation between the degree of histone acetylation and the expression level of c-Myc and certain HDAC in iPSCs. Such a close correlation was not observed in ES cells. Gene knockdown experiments showed the HDAC is possible to affect differentiated state of iPSCs. (4) Genome integrity of each iPSC was not direct cause of its developmental potential.