The transcription factor Gbx2 induces expression of Kruppel-like factor 4 to maintain and induce naive pluripotency of embryonic stem cells
The transcription factor Gbx2 induces expression of Kruppel-like factor 4 to maintain and induce naive pluripotency of embryonic stem cells
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转录因子 Gbx2 诱导 Kruppel 样因子 4 的表达，以维持和诱导胚胎干细胞的幼稚多能性
DOI：
10.1074/jbc.m117.803254
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发表时间：
2017-10-13
影响因子：
4.8
通讯作者：
Ye, Shoudong
中科院分区：
文献类型：
--
作者：
Wang, Manman;Tang, Ling;Ye, Shoudong
转录因子Gbx 2（原肠胚形成脑同源框2）是LIF/STAT 3信号通路的直接靶点，维持小鼠胚胎干细胞（mESC）自我更新，并促进小鼠上胚层干细胞（mEpiSC）重编程为幼稚多能性。然而，Gbx 2介导其对多能性影响的机制仍然未知。在这里，使用RNA-Seq方法，我们将Klf 4（Kruppel样因子4）鉴定为Gbx 2的直接靶标。功能研究表明Klf 4介导Gbx 2的自我更新促进作用，因为Klf 4表达的敲低废除了Gbx 2维持mESC未分化状态的能力。我们还发现Gbx 2在很大程度上依赖Klf 4将mEpiSC重编程为mESC样状态。总之，我们的研究揭示了Gbx 2维持和诱导幼稚多能性的机制。这些发现扩展了我们对多能性控制网络的理解，并可能为改善ESC维持和分化的培养条件的发展提供信息。
The transcription factor Gbx2 (gastrulation brain homeobox 2) is a direct target of the LIF/STAT3 signaling pathway, maintains mouse embryonic stem cell (mESC) self-renewal, and facilitates mouse epiblast stem cell (mEpiSC) reprogramming to naive pluripotency. However, the mechanism by which Gbx2 mediates its effects on pluripotency remains unknown. Here, using an RNA-Seq approach, we identified Klf4 (Kruppel-like factor 4) as a direct target of Gbx2. Functional studies indicated that Klf4 mediates the self-renewal-promoting effects of Gbx2, because knockdown of Klf4 expression abrogated the ability of Gbx2 to maintain the undifferentiated state of mESCs. We also found that Gbx2 largely depends on Klf4 to reprogram mEpiSCs to a mESC-like state. In summary, our study has uncovered a mechanism by which Gbx2 maintains and induces naive pluripotency. These findings expand our understanding of the pluripotency control network and may inform the development of culture conditions for improved ESC maintenance and differentiation.