MRC Centre for Regenerative Medicine, University of Edinburgh, Chancellors Building, 49, Little France Crescent, Edinburgh EH16 4SB, UK.
Mol Hum Reprod. 2010 Dec;16(12):880-5. doi: 10.1093/molehr/gaq091. Epub 2010 Nov 8.
Induced pluripotent stem cells (iPSCs) may be obtained by direct reprogramming of different somatic cells to a pluripotent state by forced expression of a handful of transcription factors. It was generally assumed that iPSCs are functionally equivalent to their embryonic stem cell (ESC) counterparts. Recently, a number of research groups have demonstrated that this is not the case, showing that iPSCs retain 'epigenetic memory' of the donor tissue from which they were derived and display skewed differentiation potential. This raises the question whether such cells are fit for experimental, diagnostic or therapeutic purpose. A brief survey of the literature illustrates that differences at both epigenetic and transcriptome level are observed between various pluripotent stem cell populations. Interestingly, iPSC populations with perceived 'anomalies' can be coaxed to a more ESC-like cellular state either by continuous passaging--which attenuates these epigenetic differences--or treatment with small molecules that target the machinery responsible for remodelling the genome. This suggests that the establishment of an epigenetic status approximating an ESC counterpart is largely a passive process. The mechanisms responsible remain to be established. Meanwhile, other areas of reprogramming are rapidly evolving such as, trans-differentiation of one somatic cell type to another by the forced expression of key transcription factors. When it comes to assessing their practical usefulness, the same question will also apply.
诱导多能干细胞（iPSCs）可以通过强制表达少数几个转录因子，将不同的体细胞直接重编程为多能状态而获得。人们普遍认为 iPSCs 在功能上与其胚胎干细胞（ESC）相当。最近，许多研究小组表明事实并非如此，证明 iPSCs 保留了其来源组织的“表观遗传记忆”，并表现出偏斜的分化潜能。这就提出了这样一个问题，即这些细胞是否适合用于实验、诊断或治疗目的。简要调查文献表明，各种多能干细胞群体在表观基因组和转录组水平上都存在差异。有趣的是，具有所谓“异常”的 iPSC 群体可以通过连续传代——减弱这些表观遗传差异——或用靶向负责重塑基因组的机制的小分子处理，被诱导到更类似于 ESC 的细胞状态。这表明接近 ESC 对应物的表观遗传状态的建立在很大程度上是一个被动过程。负责的机制仍有待确定。与此同时，其他重编程领域正在迅速发展，例如通过强制表达关键转录因子将一种体细胞类型转分化为另一种体细胞类型。在评估它们的实际用途时，同样的问题也将适用。
