Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, NRW, Germany.
Stem Cells. 2012 Jan;30(1):15-21. doi: 10.1002/stem.765.
Through cellular differentiation, a single cell eventually gives rise to all the various lineages of an organism. This process has traditionally been viewed as irreversible. However, nuclear transfer experiments have demonstrated that differentiated cells can be reprogrammed to form even an entire organism. Yamanaka electrified the world with the discovery that expression of only four transcription factors was sufficient to induce pluripotency in differentiated somatic cells of mammals. Expansion of this work has shown that expression of the master pluripotency gene Oct4 is sufficient to induce pluripotency in neural stem cells. In contrast to somatic cells, germline cells express Oct4 and can acquire pluripotency without the addition of exogenous transcription factors. More recently, it has been possible to also induce an alternative cell fate directly by the transdifferentiation of cells mediated by the introduction of specific transcription factors, including Oct4. Therefore, we suggest that Oct4 is the gatekeeper into a reprogramming expressway that can be directed by altering the experimental conditions.
通过细胞分化，一个单细胞最终会产生生物体的所有各种谱系。这个过程传统上被认为是不可逆转的。然而，核转移实验表明，分化细胞可以被重新编程形成甚至整个生物体。山中伸弥发现仅表达四种转录因子就足以诱导哺乳动物分化体细胞的多能性，这一发现令世界为之震惊。这项工作的扩展表明，主多能性基因 Oct4 的表达足以诱导神经干细胞的多能性。与体细胞不同，生殖细胞表达 Oct4，并且可以在不添加外源转录因子的情况下获得多能性。最近，通过引入特定的转录因子，包括 Oct4，也可以通过细胞的转分化直接诱导替代的细胞命运。因此，我们认为 Oct4 是进入重新编程高速公路的守门员，可以通过改变实验条件来进行指导。
