Continuous passages accelerate the reprogramming of mouse induced pluripotent stem cells.

Continuous passages accelerate the reprogramming of mouse induced pluripotent stem cells.
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连续传代加速小鼠诱导多能干细胞的重编程。

DOI:
10.1089/cell.2013.0067
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发表时间:
2014-01
期刊:
Cell Reprogram
影响因子:
--
通讯作者:
Lei, Lei
Lei, Lei
中科院分区:
其他
文献类型:
--
作者:
Shan, Zhi-Yan;Wu, Yan-Shuang;Li, Xue;Shen, Xing-Hui;Wang, Zhen-Dong;Liu, Zhong-Hua;Shen, Jing-Ling;Lei, Lei

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诱导多能干细胞(iPSC)通常是通过转录因子混合物转导对体细胞进行重编程而产生的。然而,该过程的低效率使得iPSC远离干细胞生物学的临床应用研究。我们的研究表明,连续传代提高了重编程的效率。与传统的 iPSC 建立方法相比,早期重编程过程中连续传代可产生更多的胚胎干细胞 (ESC) 样克隆。这些早期克隆与真正的 ESC 克隆没有区别,与经典 iPSC 诱导衍生的细胞相比,它们更接近完全重编程的细胞,后者增加了多能基因标记的表达以及 Oct4 和 Nanog 的去甲基化水平。这些结果表明,完全重编程是一个渐进的过程,不仅仅在内源性多能性相关基因激活时结束。连续传代可以增加诱导细胞的多能性,并加速表观遗传修饰的重编程过程。简而言之,我们提供了一种先进的策略来加速重编程并高效、快速地生成更接近完全重编程的 iPSC。
Induced pluripotent stem cells (iPSCs) are usually generated by reprogramming somatic cells through transduction with a transcription factor cocktail. However, the low efficiency of this procedure has kept iPSCs away from the study of the clinical application of stem cell biology. Our research shows that continuous passage increases the efficiency of reprogramming. Compared with conventional method of establishment of iPSCs, more embryonic stem cell (ESC)-like clones are generated by continuous passage during early reprogramming. These inchoate clones, indistinguishable from genuine ESC clones, are closer to fully reprogrammed cells compared with those derived from classical iPSC induction, which increased the expression of pluripotent gene markers and the levels of demethylation of Oct4 and Nanog. These results suggested that full reprogramming is a gradual process that does not merely end at the point of the activation of endogenous pluripotency-associated genes. Continuous passage could increase the pluripotency of induced cells and accelerate the process of reprogramming by epigenetic modification. In brief, we have provided an advanced strategy to accelerate the reprogramming and generate more nearly fully reprogrammed iPSCs efficiently and rapidly.
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