Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Röntgenstrasse 20, 48149 Münster, Germany.
Nat Cell Biol. 2013 Sep;15(9):1089-97. doi: 10.1038/ncb2816. Epub 2013 Aug 11.
Oct4A is a core component of the regulatory network of pluripotent cells, and by itself can reprogram neural stem cells into pluripotent cells in mice and humans. However, its role in defining totipotency and inducing pluripotency during embryonic development is still unclear. We genetically eliminated maternal Oct4A using a Cre/loxP approach in mouse and found that the establishment of totipotency was not affected, as shown by the generation of live pups. After complete inactivation of both maternal and zygotic Oct4A expression, the embryos still formed Oct4-GFP- and Nanog-expressing inner cell masses, albeit non-pluripotent, indicating that Oct4A is not a determinant for the pluripotent cell lineage separation. Interestingly, Oct4A-deficient oocytes were able to reprogram fibroblasts into pluripotent cells. Our results clearly demonstrate that, in contrast to its role in the maintenance of pluripotency, maternal Oct4A is not crucial for either the establishment of totipotency in embryos, or the induction of pluripotency in somatic cells using oocytes.
Oct4A 是多能性细胞调控网络的核心组成部分，它本身可以将神经干细胞重编程为小鼠和人类的多能性细胞。然而，其在胚胎发育过程中定义全能性和诱导多能性的作用尚不清楚。我们使用 Cre/loxP 方法在小鼠中遗传消除母源 Oct4A，发现全能性的建立没有受到影响，这表现为活幼仔的产生。在完全消除母源和合子源 Oct4A 表达后，胚胎仍然形成 Oct4-GFP 和 Nanog 表达的内细胞团，尽管不是多能性的，表明 Oct4A 不是多能性细胞谱系分离的决定因素。有趣的是，缺乏 Oct4A 的卵母细胞能够将成纤维细胞重编程为多能性细胞。我们的结果清楚地表明，与维持多能性的作用相反，母源 Oct4A 对于胚胎全能性的建立或使用卵母细胞诱导体细胞多能性都不是至关重要的。
