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首页> 外文期刊>Current Biology: CB >A High Proliferation Rate Is Required for Cell Reprogramming and Maintenance of Human Embryonic Stem Cell Identity
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A High Proliferation Rate Is Required for Cell Reprogramming and Maintenance of Human Embryonic Stem Cell Identity

机译：细胞重编程和维持人类胚胎干细胞特性需要高增殖率

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Human embryonic stem (hES) cells show an atypical cell-cycle regulation characterized by a high proliferation rate and a short G1 phase [[1] and [2]]. In fact, a shortened G1 phase might protect ES cells from external signals inducing differentiation, as shown for certain stem cells [3]. It has been suggested that self-renewal and pluripotency are intimately linked to cell-cycle regulation in ES cells [[4], [5] and [6]], although little is known about the overall importance of the cell-cycle machinery in maintaining ES cell identity. An appealing model to address whether the acquisition of stem cell properties is linked to cell-cycle regulation emerged with the ability to generate induced pluripotent stem (iPS) cells by expression of defined transcription factors [[7], [8], [9], [10] and [11]]. Here, we show that the characteristic cell-cycle signature of hES cells is acquired as an early event in cell reprogramming. We demonstrate that induction of cell proliferation increases reprogramming efficiency, whereas cell-cycle arrest inhibits successful reprogramming. Furthermore, we show that cell-cycle arrest is sufficient to drive hES cells toward irreversible differentiation. Our results establish a link that intertwines the mechanisms of cell-cycle control with the mechanisms underlying the acquisition and maintenance of ES cell identity.
机译：人类胚胎干（hES）细胞表现出非典型的细胞周期调控，其特征是高增殖率和短G1期[[1]和[2]]。实际上，缩短的G1期可能保护ES细胞免受诱导分化的外部信号的影响，如某些干细胞所示[3]。有人指出，自我更新和多能性与ES细胞的细胞周期调控密切相关[[4]，[5]和[6]]，尽管人们对细胞周期机制在人​​类中的整体重要性知之甚少。维持ES细胞身份。一个有吸引力的模型解决了干细胞特性的获取是否与细胞周期调控相关的问题，该模型具有通过表达定义的转录因子产生诱导性多能干（iPS）细胞的能力[[7]，[8]，[9] ，[10]和[11]]。在这里，我们表明，hES细胞的特征性细胞周期特征是作为细胞重编程中的早期事件而获得的。我们证明诱导细胞增殖增加了重新编程的效率，而细胞周期停滞抑制了成功的重新编程。此外，我们表明细胞周期停滞足以驱动hES细胞走向不可逆的分化。我们的结果建立了一个链接，该链接将细胞周期控制的机制与ES细胞身份的获取和维持所依据的机制交织在一起。

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