Author/Authors :
Jian Shu، نويسنده , , Chen Wu، نويسنده , , Yetao Wu، نويسنده , , Zhiyuan Li and Peiwu Wang ، نويسنده , , Sida Shao، نويسنده , , Wenhui Zhao، نويسنده , , Xing Tang، نويسنده , , Huan Yang، نويسنده , , Lijun Shen، نويسنده , , Xiaohan Zuo، نويسنده , , Weifeng Yang، نويسنده , , Yan Shi، نويسنده , , Xiaochun Chi، نويسنده , , Hongquan Zhang، نويسنده , , Ge Gao، نويسنده , , Youmin Shu، نويسنده , , Kehu Yuan، نويسنده , , Weiwu He، نويسنده , , Chao Tang، نويسنده , , Yang Zhao، نويسنده , , et al.، نويسنده ,
Abstract :
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.
