Nandan Mandayam O, Yang Vincent W
Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Histol Histopathol. 2009 Oct;24(10):1343-55. doi: 10.14670/HH-24.1343.
The potential for clinical application of pluripotent embryonic stem cells is immense but hampered by moral and ethical complications. Recent advances in the reprogramming of somatic cells by defined factors to a state that resemble embryonic stem cells have created tremendous excitement in the field. Four factors, Sox2, Oct4, Klf4 and c-Myc, when exogenously introduced into somatic cells, can lead to the formation of induced pluripotent stem (iPS) cells that have the capacity for self-renewal and differentiation into tissues of all three germ layers. In this review, we focus on the role of Krüppel-like factors (KLFs) in regulating somatic cell reprogramming. KLFs are zinc finger-containing transcription factors with diverse biological functions. We first provide an overview of the KLF family of regulatory proteins, paying special attention to the established biological and biochemical functions of KLF4 and KLF5. We then review the role of KLFs in somatic cell reprogramming and delineate the putative mechanism by which KLFs participates the establishment and self-renewal of iPS cells. Further research is likely to provide additional insight into the mechanisms of somatic cell reprogramming and refinement of the technique with which to generate clinically relevant iPS cells.
多能胚胎干细胞的临床应用潜力巨大,但受到道德和伦理问题的阻碍。最近,通过特定因子将体细胞重编程为类似胚胎干细胞的状态取得了进展,这在该领域引起了极大的轰动。当将Sox2、Oct4、Klf4和c-Myc这四种因子外源导入体细胞时,可导致诱导多能干细胞(iPS细胞)的形成,这些细胞具有自我更新能力,并能分化为所有三个胚层的组织。在本综述中,我们重点关注Krüppel样因子(KLFs)在调节体细胞重编程中的作用。KLFs是具有多种生物学功能的含锌指转录因子。我们首先概述KLF调节蛋白家族,特别关注已确定的KLF4和KLF5的生物学和生化功能。然后,我们回顾KLFs在体细胞重编程中的作用,并描述KLFs参与iPS细胞建立和自我更新的假定机制。进一步的研究可能会为体细胞重编程的机制提供更多见解,并改进生成临床相关iPS细胞的技术。