Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Int J Mol Sci. 2018 Mar 21;19(4):930. doi: 10.3390/ijms19040930.
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. The pattern of expressed genes, DNA methylation, and covalent histone modifications in iPS cells are very similar to those in ES cells. However, it has recently been shown that, following the reprogramming of mouse/human iPS cells, epigenetic memory is inherited from the parental cells. These findings suggest that the phenotype of iPS cells may be influenced by their cells of origin and that their skewed differentiation potential may prove useful in the generation of differentiated cell types that are currently difficult to produce from ES/iPS cells for the treatment of human diseases. Our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors combined with tissue-specific selection. iTS cells are cells that inherit numerous components of epigenetic memory from donor tissue and acquire self-renewal potential. This review describes the "epigenetic memory" phenomenon in iPS and iTS cells and the possible clinical applications of these stem cells.
诱导多能干细胞(iPS 细胞)对于克服大多数与胚胎干细胞(ES 细胞)相关的伦理问题具有重要意义。iPS 细胞中表达基因、DNA 甲基化和组蛋白共价修饰的模式与 ES 细胞非常相似。然而,最近的研究表明,在重编程小鼠/人类 iPS 细胞后,表观遗传记忆会从亲代细胞遗传。这些发现表明,iPS 细胞的表型可能受其起源细胞的影响,其偏分化潜能可能在生成目前难以从 ES/iPS 细胞产生的用于治疗人类疾病的分化细胞类型方面具有应用价值。我们最近的研究表明,通过瞬时过表达重编程因子并结合组织特异性选择,可以产生诱导组织特异性干细胞(iTS 细胞)。iTS 细胞是从供体组织中继承了许多表观遗传记忆成分并获得自我更新能力的细胞。本综述描述了 iPS 和 iTS 细胞中的“表观遗传记忆”现象以及这些干细胞的可能临床应用。