van den Hurk Mark, Kenis Gunter, Bardy Cedric, van den Hove Daniel L, Gage Fred H, Steinbusch Harry W, Rutten Bart P
Department of Psychiatry & Neuropsychology, Division of Translational Neuroscience, Maastricht University, Maastricht, 6200 MD, The Netherlands.
European Graduate School of Neuroscience (EURON), Maastricht University, Maastricht, 6200 MD, The Netherlands.
Epigenomics. 2016 Aug;8(8):1131-49. doi: 10.2217/epi-2016-0032. Epub 2016 Jul 15.
Enforced ectopic expression of a cocktail of pluripotency-associated genes such as Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). The remarkable proliferation ability of iPSCs and their aptitude to redifferentiate into any cell lineage makes these cells a promising tool for generating a variety of human tissue in vitro. Yet, pluripotency induction is an inefficient process, as cells undergoing reprogramming need to overcome developmentally imposed epigenetic barriers. Recent work has shed new light on the molecular mechanisms that drive the reprogramming of somatic cells to iPSCs. Here, we present current knowledge on the transcriptional and epigenetic regulation of pluripotency induction and discuss how variability in epigenetic states impacts iPSCs' inherent biological properties.
强制异位表达多能性相关基因组合，如Oct4、Sox2、Klf4和c-Myc，可将体细胞重编程为诱导多能干细胞（iPSC）。iPSC具有显著的增殖能力，且能够重新分化为任何细胞谱系，这使得这些细胞成为体外生成多种人体组织的有前景的工具。然而，多能性诱导是一个低效的过程，因为经历重编程的细胞需要克服发育过程中形成的表观遗传障碍。最近的研究为驱动体细胞重编程为iPSC的分子机制提供了新的线索。在此，我们介绍了关于多能性诱导的转录和表观遗传调控的当前知识，并讨论了表观遗传状态的变异性如何影响iPSC的固有生物学特性。
