Establishment of totipotency does not depend on Oct4A.
Establishment of totipotency does not depend on Oct4A.
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DOI：
10.1038/ncb2816
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发表时间：
2013-09
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Oct 4A是多能细胞调控网络的核心组成部分，它本身可以将小鼠和人类的神经干细胞重新编程为多能细胞。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仍不清楚。我们在小鼠中使用Cre-lox方法遗传消除了母体Oct 4A，并发现全能性的建立不受影响，如活幼崽的产生所示。在母体和合子Oct 4A表达完全失活后，胚胎仍然形成表达Oct 4-GFP和Nanog的内细胞团，尽管是非多能的，表明Oct 4A不是多能细胞谱系分离的决定因素。有趣的是，Oct 4A缺陷的卵母细胞能够将成纤维细胞重编程为多能细胞。我们的研究结果清楚地表明，与其在维持多能性中的作用相反，母体Oct 4A对于在胚胎中建立全能性和使用卵母细胞诱导体细胞中的多能性都是至关重要的。
Oct4A is a core component of the regulatory network of pluripotent cells, and by itself can reprogram neural stem cells into pluripotent cells in mouse 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-lox 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 crucial for neither the establishment of totipotency in embryos, nor the induction of pluripotency in somatic cells using oocytes.
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