Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2.

Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2.
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DOI:
10.1002/stem.240
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发表时间:
2009-12
期刊:
影响因子:
5.2
通讯作者:
Ding, Sheng
Ding, Sheng
中科院分区:
医学2区
文献类型:
--
作者:
Li, Wenlin;Zhou, Hongyan;Abujarour, Ramzey;Zhu, Saiyong;Joo, Jin Young;Lin, Tongxiang;Hao, Ergeng;Schoeler, Hans R.;Hayek, Alberto;Ding, Sheng

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诱导多能干细胞技术在再生医学领域的潜在应用引起了人们极大的兴趣。本文报道了一种特异性的糖原合成酶激酶3(GSK-3)抑制剂CHIR 99021,能够诱导仅由Oct 4和Klf 4两种因子转导的小鼠胚胎成纤维细胞(MEFs)重编程。当与Parnate(也称为反苯环丙胺)(赖氨酸特异性脱甲基酶1的抑制剂)组合时,CHIR 99021可以导致用Oct 4和Klf 4两种因子转导的人原代角质形成细胞的重编程。据我们所知,这是第一次从体细胞中产生人iPS细胞而不表达外源Sox 2。我们的研究表明,GSK-3抑制剂可能具有替代小鼠和人类重编程中的转录因子的一般应用。
Induced pluripotent stem cell technology has attracted enormous interests for potential application in regenerative medicine. Here, we reported that a specific glycogen synthase kinase 3 (GSK-3) inhibitor, CHIR99021, can induce the reprogramming of mouse embryonic fibroblasts (MEFs) transduced by only Oct4 and Klf4 two factors. When combined with Parnate (also named tranylcypromine), an inhibitor of lysine-specific demethylase 1, CHIR99021 can result in the reprogramming of human primary keratinocyte transducted with Oct4 and Klf4 two factors. To our knowledge, this is the first time to generate human iPS cells from somatic cells without exogenous Sox2 expression. Our studies suggest that the GSK-3 inhibitor might have a general application to replace transcription factors in both mouse and human reprogramming.
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