Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell. 2013 Mar 14;152(6):1324-43. doi: 10.1016/j.cell.2013.02.043.
Reprogramming to induced pluripotent stem cells (iPSCs) proceeds in a stepwise manner with reprogramming factor binding, transcription, and chromatin states changing during transitions. Evidence is emerging that epigenetic priming events early in the process may be critical for pluripotency induction later. Chromatin and its regulators are important controllers of reprogramming, and reprogramming factor levels, stoichiometry, and extracellular conditions influence the outcome. The rapid progress in characterizing reprogramming is benefiting applications of iPSCs and is already enabling the rational design of novel reprogramming factor cocktails. However, recent studies have also uncovered an epigenetic instability of the X chromosome in human iPSCs that warrants careful consideration.
重编程为诱导多能干细胞 (iPSCs) 是一个逐步进行的过程,在此过程中,重编程因子结合、转录和染色质状态在转变过程中发生变化。有证据表明,在这个过程的早期,表观遗传引发事件对于后期的多能性诱导可能是至关重要的。染色质及其调控因子是重编程的重要控制器,而重编程因子水平、化学计量和细胞外条件会影响结果。在对重编程进行特征描述方面的快速进展使 iPSCs 的应用受益,并且已经能够实现新型重编程因子鸡尾酒的合理设计。然而,最近的研究还揭示了人类 iPSCs 中 X 染色体的表观遗传不稳定性,这需要仔细考虑。