Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Biochemistry, University of Cambridge, Cambridge, UK.
Nat Cell Biol. 2013 Jun;15(6):579-90. doi: 10.1038/ncb2742. Epub 2013 Apr 30.
Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.
Oct4 被认为是多能干细胞自我更新的主要转录因子，但它的生物学功能仍知之甚少。在这里，我们使用诱导多能性的过程研究了 Oct4 的作用。我们发现，多能性进入需要一个确定的胚胎干细胞（ESC）水平的 Oct4。然而，一旦多能性建立，Oct4 水平可以降低至七倍而不会失去自我更新。出乎意料的是，持续表达 ESC 水平 Oct4 的细胞能够强有力地分化为所有胚胎谱系和生殖系。相比之下，Oct4 水平低的细胞在分化方面存在缺陷，在没有多能性培养要求的情况下表现出原始多能性基因的表达。将 Oct4 表达恢复到 ESC 水平挽救了这些细胞限制原始多能性基因表达和分化的能力。总之，一个确定的 Oct4 水平控制着原始多能性的建立以及向所有胚胎谱系的分化。
