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首页> 外文期刊>Current Biology: CB >Nanog Overcomes Reprogramming Barriers and Induces Pluripotency in Minimal Conditions
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Nanog Overcomes Reprogramming Barriers and Induces Pluripotency in Minimal Conditions

机译：Nanog在最小的条件下克服了重新编程的障碍并诱导了多能性。

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Induced pluripotency requires the expression of defined factors and culture conditions that support the self-renewal of embryonic stem (ES) cells [1]. Small molecule inhibition of MAP kinase (MEK) and glycogen synthase kinase 3 (GSK3) with LIF (2i/LIF) provides an optimal culture environment for mouse ES cells [2] and promotes transition to naive pluripotency in partially reprogrammed (pre-iPS) cells [3]. Here we show that 2i/LIF treatment in clonal lines of pre-iPS cells results in the activation of endogenous Nanog and rapid downregulation of retroviral Oct4 expression. Nanog enables somatic cell reprogramming in serum-free medium supplemented with LIF, a culture condition which does not support induced pluripotency or the self-renewal of ES cells, and is sufficient to reprogram epiblast-derived stem cells to naive pluripotency in serum-free medium alone. Nanog also enhances reprogramming in cooperation with kinase inhibition or 5-aza-cytidine, a small molecule inhibitor of DNA methylation. These results highlight the capacity of Nanog to overcome multiple barriers to reprogramming and reveal a synergy between Nanog and chemical inhibitors that promote reprogramming. We conclude that Nanog induces pluripotency in minimal conditions. This provides a strategy for imposing naive pluripotency in mammalian cells independently of species-specific culture requirements. Highlights: Response to dual kinase inhibition (2i) is examined in clonal lines of pre-iPS cells Nanog enhances reprogramming in synergy with 2i or inhibition of DNA methylation Nanog counteracts p-Erk and high levels of Oct4 during somatic cell reprogramming Nanog is sufficient to reprogram epiblast-derived stem cells to naive pluripotency
机译：诱导多能性需要表达确定的因子和培养条件以支持胚胎干（ES）细胞的自我更新[1]。 LIF（2i / LIF）对MAP激酶（MEK）和糖原合酶激酶3（GSK3）的小分子抑制为小鼠ES细胞提供了最佳的培养环境[2]，并促进了部分重编程（pre-iPS）到幼稚多能性的转变。细胞[3]。在这里，我们显示preiPS细胞的克隆系中的2i / LIF处理导致内源性Nanog的激活和逆转录病毒Oct4表达的快速下调。 Nanog可以在补充了LIF的无血清培养基中对体细胞进行重编程，LIF是一种不支持诱导多能性或ES细胞自我更新的培养条件，并且足以在无血清培养基中将源自上皮细胞的干细胞重编程为幼稚的多能性。单独。 Nanog还与激酶抑制或5-甲基氮杂胞苷（一种DNA甲基化的小分子抑制剂）合作，增强了重编程能力。这些结果突出了Nanog克服重编程的多重障碍的能力，并揭示了Nanog与促进重编程的化学抑制剂之间的协同作用。我们得出的结论是，Nanog在最小条件下诱导多能性。这提供了一种独立于物种特定培养要求而在哺乳动物细胞中施加幼稚多能性的策略。亮点：在iPS前细胞的克隆系中检查了对双重激酶抑制（2i）的响应Nanog增强了与2i协同作用的重编程，或者抑制DNA甲基化Nanog抵消了p-Erk，在体细胞重编程过程中高水平的Oct4足以重编程上皮细胞衍生的干细胞至幼稚多能性

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