Parisi Silvia, Passaro Fabiana, Aloia Luigi, Manabe Ichiro, Nagai Ryozo, Pastore Lucio, Russo Tommaso
CEINGE Biotecnologie Avanzate, 80145 Napoli, Italy.
J Cell Sci. 2008 Aug 15;121(Pt 16):2629-34. doi: 10.1242/jcs.027599. Epub 2008 Jul 24.
Self-renewal of embryonic stem cells (ESCs) is maintained by a complex regulatory mechanism involving transcription factors Oct3/4 (Pou5f1), Nanog and Sox2. Here, we report that Klf5, a Zn-finger transcription factor of the Kruppel-like family, is involved in ESC self-renewal. Klf5 is expressed in mouse ESCs, blastocysts and primordial germ cells, and its knockdown by RNA interference alters the molecular phenotype of ESCs, thereby preventing their correct differentiation. The ability of Klf5 to maintain ESCs in the undifferentiated state is supported by the finding that differentiation of ESCs is prevented when Klf5 is constitutively expressed. Maintenance of the undifferentiated state by Klf5 is, at least in part, due to the control of Nanog and Oct3/4 transcription, because Klf5 directly binds to the promoters of these genes and regulates their transcription.
胚胎干细胞(ESC)的自我更新由一个复杂的调控机制维持,该机制涉及转录因子Oct3/4(Pou5f1)、Nanog和Sox2。在此,我们报告Klf5,一种Kruppel样家族的锌指转录因子,参与了ESC的自我更新。Klf5在小鼠ESC、囊胚和原始生殖细胞中表达,通过RNA干扰敲低其表达会改变ESC的分子表型,从而阻止其正确分化。当Klf5组成型表达时可防止ESC分化,这一发现支持了Klf5将ESC维持在未分化状态的能力。Klf5对未分化状态的维持至少部分是由于对Nanog和Oct3/4转录的调控,因为Klf5直接结合这些基因的启动子并调节它们的转录。