MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China.
Cell. 2013 May 23;153(5):963-75. doi: 10.1016/j.cell.2013.05.001.
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.
重编程因子主要是从富含胚胎干细胞（ESC）和多能性相关因子的胚胎干细胞中鉴定出来的。在这里，我们报告说，在小鼠体细胞重编程过程中，可以使用谱系特异性标志物诱导多能性，这些标志物是与 ESC 身份竞争的多能性，其中大多数在 ESC 中并不丰富。我们发现，多能性的核心调控因子 OCT4 和 SOX2 可以分别被参与中胚层（ME）和外胚层（ECT）特化的谱系特异性标志物所取代。OCT4 和它的替代物降低了一组 ECT 基因的表达水平，而 SOX2 和它的替代物在重编程过程中抑制了一组 ME 基因。令人惊讶的是，这两种相互拮抗的谱系特异性标志物可以在缺乏 OCT4 和 SOX2 的情况下协同诱导多能性。我们的研究提出了一个“跷跷板模型”，即在使用多能性因子和/或拮抗谱系特异性标志物建立平衡的情况下，可以促进重编程。
