Induction of Pluripotency in Mouse Somatic Cells with Lineage Specifiers

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• 作者：Jian Shu¹ ; ³ ; ⁹ ; Chen Wu³ ; ⁶ ; ⁹ ; Yetao Wu³ ; ⁶ ; ⁹ ; Zhiyuan Li² ; ⁷ ; ⁹ ; Sida Shao¹ ; Wenhui Zhao¹ ; ³ ; Xing Tang⁴ ; Huan Yang³ ; ⁶ ; Lijun Shen¹ ; Xiaohan Zuo³ ; ⁶ ; Weifeng Yang¹ ; Yan Shi⁶ ; Xiaochun Chi⁵ ; Hongquan Zhang⁵ ; Ge Gao⁴ ; Youmin Shu⁸ ; Kehu Yuan⁸ ; Weiwu He⁸ ; Chao Tang² ; ³ ; ^{tangc@pku.edu.cn} ; Yang Zhao¹ ; ³ ; Hongkui Deng¹ ; ³ ; ⁶ ; ^{hongkui_deng@pku.edu.cn}
• 刊名：Cell
• 出版年：2013
• 出版时间：23 May, 2013
• 年：2013
• 卷：153
• 期：5
• 页码：963-975
• 全文大小：3564 K

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Summary

The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a ¡°seesaw model¡± in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.