家兔Naïve态胚胎干细胞与种质传递机制的研究

胚胎干细胞（ES）分为Primed和Naïve态两种类型，仅Naïve态ES具备种质传递的潜能。目前未见报道家兔胚胎干细胞(rbES)能分化成生殖细胞并种质传递。我们培育出Primed和Naïve态两种rbES细胞系。项目拟将探索Naïve态rbES捕获、自我更新、分化与种质传递的分子机制:（1）探索维持Naïve态rbES网络状信号通路的调控机制，包括在MEK/ERK抑制下bFGF诱导PI3K/AKT通路，PKCi抑制NuRD相关基因的表达，3i协同的信号通路调控，（2）采用ChiP-Seq和RNA-Seq确立Naïve态rbES的表观遗传学与基因表达模式，（3）探索Naïve态rbES分化生殖细胞的潜能与传递规律。目的是揭示Naïve态rbES捕获、维持与分化的分子调控。家兔是重要的经济物种和实验动物。本研究将为大家畜ES的研究提供相应的依据与借鉴，促进我国家畜基因改良与畜牧业的发展。

Embryonic stem cells (ES) are classified into both primed and naïve states, while only naïve state possesses the potential of germline transmission. We will study the molecular mechanism of derivation, self-renewal, differentiation and germline transmission in rabbit ES (rbES). Rabbit is considered as important farm and laboratory animals. However, there is not a research team to date that can prove the differentiation pluripotency, which rbES can continue to differentiate into the specific germ cells, and finally have the potentials to transmit into the germplasm (germline). We have successfully derived both primed and naïve rbES line in our previous study, which lays a scientific foundation for a new study. We will continue to (1) study the mechanisms of circuit signal pathways in controlling naïve rbES, including bFGF induced PI3K/AKT signal pathway under MEK/ERK inhibition, PKCi repression of NuRD complex gene expression and synergistic regulation of signal pathways, (2) evaluate its specific pattern of gene expression and model of epigenetic regulation in naïve rbES by ChIP-Seq and RNA-Seq, and (3) explore self-renewal of naïve rbES and further their ability of germline transmission. The success in this study will provide theoretic basis for ES study in large farm animals, which promotes the development of genetic improvement and production of animal husbandry in China.