Lengner Christopher J, Camargo Fernando D, Hochedlinger Konrad, Welstead G Grant, Zaidi Samir, Gokhale Sumita, Scholer Hans R, Tomilin Alexey, Jaenisch Rudolf
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA.
Cell Stem Cell. 2007 Oct 11;1(4):403-15. doi: 10.1016/j.stem.2007.07.020.
The Pou domain containing transcription factor Oct4 is a well-established regulator of pluripotency in the inner cell mass of the mammalian blastocyst as well as in embryonic stem cells. While it has been shown that the Oct4 gene is inactivated through a series of epigenetic modifications following implantation, recent studies have detected Oct4 activity in a variety of somatic stem cells and tumor cells. Based on these observations it has been suggested that Oct4 may also function in maintaining self-renewal of somatic stem cells and, in addition, may promote tumor formation. We employed a genetic approach to determine whether Oct4 is important for maintaining pluripotency in the stem cell compartments of several somatic tissues including the intestinal epithelium, bone marrow (hematopoietic and mesenchymal lineages), hair follicle, brain, and liver. Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal.
含Pou结构域的转录因子Oct4是哺乳动物囊胚内细胞团以及胚胎干细胞中多能性的公认调节因子。虽然已经表明Oct4基因在植入后通过一系列表观遗传修饰而失活,但最近的研究在多种体细胞干细胞和肿瘤细胞中检测到了Oct4活性。基于这些观察结果,有人提出Oct4可能还在维持体细胞干细胞的自我更新中发挥作用,此外,可能促进肿瘤形成。我们采用遗传学方法来确定Oct4对于维持包括肠上皮、骨髓(造血和间充质谱系)、毛囊、脑和肝脏在内的几种体细胞组织的干细胞区室中的多能性是否重要。这些组织中的Oct4基因缺失未显示出体内稳态或再生能力的异常。我们得出结论,Oct4对于成年哺乳动物体细胞干细胞的自我更新和维持都是可有可无的。