A core Klf circuitry regulates self-renewal of embryonic stem cells
A core Klf circuitry regulates self-renewal of embryonic stem cells
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DOI：
10.1038/ncb1698
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发表时间：
2008-03-01
影响因子：
21.3
通讯作者：
Ng, Huck-Hui
中科院分区：
文献类型：
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作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
胚胎干细胞（ES）具有无限自我更新和维持多能性的能力。这些特性需要转录因子来指定ES细胞的基因表达程序。已经有可能用四种转录因子的组合将体细胞的高度分化状态逆转回多能状态：Klf 4是所需的重编程因子之一，与Oct 4，Sox 2和c-Myc一起。ES细胞的自我更新和多能性的维持需要Oct 4、Sox 2和c-Myc，但Klf 4是必需的。在这里，我们表明，Kruppel样因子所需的自我更新的ES细胞。Klf 2、Klf 4和Klf 5的同时消耗导致ES细胞分化。染色质免疫沉淀结合微阵列分析表明，这些Klf蛋白有许多共同的Nanog靶点，表明这些因子之间存在密切的功能关系。Klf的三重RNA干扰（RNAi）后的表达分析显示它们调节关键的多能性基因，如Nanog。总之，我们的研究提供了新的见解，核心Klf电路如何整合到Nanog转录网络，以指定基因表达是独特的ES细胞。
Embryonic stem (ES) cells are unique in their ability to self-renew indefinitely and maintain pluripotency. These properties require transcription factors that specify the gene expression programme of ES cells. It has been possible to reverse the highly differentiated state of somatic cells back to a pluripotent state with a combination of four transcription factors: Klf4 is one of the reprogramming factors required, in conjunction with Oct4, Sox2 and c-Myc. Maintenance of self-renewal and pluripotency of ES cells requires Oct4, Sox2 and c-Myc, but Klf4 is dispensable. Here, we show that Kruppel- like factors are required for the self-renewal of ES cells. Simultaneous depletion of Klf2, Klf4 and Klf5 lead to ES cell differentiation. Chromatin immunoprecipitation coupled to microarray assay reveals that these Klf proteins share many common targets of Nanog, suggesting a close functional relationship between these factors. Expression analysis after triple RNA interference (RNAi) of the Klfs shows that they regulate key pluripotency genes, such as Nanog. Taken together, our study provides new insight into how the core Klf circuitry integrates into the Nanog transcriptional network to specify gene expression that is unique to ES cells.