再度、書きます。お題目を訳してどうするの？もう、みんな、そんなところはわかっています。 ＴＳ，ＥＳ，ＥPiＳ を人工的に誘導できるということは、ＴＦｓネットワークが一旦、落ち着く状態になるからではないの？ ＴＳ，ＥＳ，ＥPiＳを現実に、人が誘導できるから、こうしたＴＦｓネットワークの動きがわかってきたのでしょう？ つまり、以下の英文部分が大事なのではないですか？コメントください！ ＞The dynamic changes in TF binding between mESCs and EpiSCs may support the existence of such an intermediate state as defined by a stable TF network
In animal evolution, the number of TFs encoded in the genome has increased with the number of cell types. How is the acquisition of an evolutionarily novel cell type achieved with respect to the underlying TF network? The placenta is an evolutionary novelty in mammals, and thus the TSC-specific TF network is an evolutionary novelty of placental mammals. However, very few novel genes that are unique to mammals function in placental development. Peg10, which derives from a retrotransposon, is a rare example of this category (Ono et al., 2006). By contrast, the molecular functions tend to be highly conserved during evolution. Sox2 is a member of the group B1 Sox family, which is conserved in invertebrates. In Drosophila, the group B1 Sox family members function in neuronal development, and neuronal function is conserved in mammalian group B1 members Sox1, Sox2 and Sox3 (Kamachi and Kondoh, 2013). The amino acid sequences of the Drosophila and mammalian group B1 members share homology only in the HMG box (Niwa et al., 2016). However, mouse Sox2 can be replaced by Drosophila SoxN in maintaining the pluripotency of mESCs, indicating that the conserved function of the group B1 Sox family is effective even in mESCs (Niwa et al., 2016). Since there is no evidence that a pluripotent cell population exists in developing Drosophila, then it follows that the pluripotent state is an evolutionary novelty in vertebrates, especially mammals. Therefore, the specific function of Sox2 in mESCs must be co-opted from its evolutionarily conserved function.
The use of evolutionarily conserved TFs to define novel cell types suggests that the evolutionary acquisition of novelty could derive from the establishment of new combinations of TFs in a network, rather than the acquisition of new TF functions. In the new network, each TF interconnects with other TFs by acquiring new enhancers with little or no acquisition of new molecular function. The flexibility of the connection between the extracellular signals and the TF networks, and between the TF networks and the target genes, would allow a new combination of regulatory elements to evolve. The evolution of the cis-regulatory elements was emphasized in a genetic theory of morphological evolution (Carroll, 2008), and the gain-of-function of cis-regulatory elements can occur by insertion of new elements without affecting the ancestral regulatory element, allowing co-optional use of the genes for novel functions (Peter and Davidson, 2011). In addition, the combined activity of multiple TFs on a super-enhancer to recruit the Mediator complex could make it relatively straightforward to achieve new synergistic functions among a novel combination of TFs. These events would enable a new combination of TFs in the network to be established, which in turn could lead to the specification of an evolutionarily novel cell type. Among the TFs of the TSC-specific network, the evolutionarily conserved functions of Sox2, Eomes and Cdx2 are found in neuroectoderm, mesoendoderm and definitive endoderm, respectively (Box 1, Glossary) (Sasai, 2001; Beck and Stringer, 2010; Probst and Arnold, 2017), but they cooperate together to define an evolutionarily new cell type, the trophoblast. Such flexibility in the combination of TFs could be a result of the flexible design of a TF network.