Identification of Ccr4-Not Complex Components as Regulators of Transition from Partial to Genuine Induced Pluripotent Stem Cells
Identification of Ccr4-Not Complex Components as Regulators of Transition from Partial to Genuine Induced Pluripotent Stem Cells
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DOI：
10.1089/scd.2013.0326
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发表时间：
2014-09-15
影响因子：
4
通讯作者：
Okuda, Akihiko
中科院分区：
文献类型：
--
作者：
Kamon, Masayoshi;Katano, Miyuki;Okuda, Akihiko
体细胞可以在一定的条件下被重新编程为诱导多能干细胞(IPSCs)。然而，经过IPSC诱导的大量细胞偏离了主要的重新编程途径，并被永垂不朽为部分IPSC。这些部分IPSCs可以通过暴露在基态条件下成为真正的IPSCs。然而，这种转化只可能用于小鼠的部分IPSCs，而不适用于人类细胞。此外，这种转化的分子基础完全未知。因此，我们在全基因组范围内进行了一系列的筛选，以确定参与部分IPSCs向真正IPSCs转化的基因。这一筛选导致了CCR4的核心成分之一Cnot2的鉴定-Not Complex。随后的分析显示，其他核心组成部分Cnot1和CNOT3也促进了转换。因此，我们的数据揭示了CCR4核心组件的一个新角色--作为从部分IPSC向真正的IPSC过渡的调节器并不复杂。
Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by defined factors. However, substantial cell numbers subjected to iPSC induction stray from the main reprogramming route and are immortalized as partial iPSCs. These partial iPSCs can become genuine iPSCs by exposure to the ground state condition. However, such conversion is only possible for mouse partial iPSCs, and it is not applicable to human cells. Moreover, the molecular basis of this conversion is completely unknown. Therefore, we performed genome-wide screening with a piggyBac vector to identify genes involved in conversion from partial to genuine iPSCs. This screening led to identification of Cnot2, one of the core components of the Ccr4-Not complex. Subsequent analyses revealed that other core components, Cnot1 and Cnot3, also contributed to the conversion. Thus, our data have uncovered a novel role of core components of the Ccr4-Not complex as regulators of transition from partial to genuine iPSCs.