哺乳动物早期胚胎发育伴随着细胞命运的决定和细胞的分裂与增殖。细胞命运是由基因和表观遗传学的调控决定的，而细胞的分裂与增殖则要依赖于细胞内的代谢活动。基因和表观的调控与代谢调控是如何协同作用，共同促进早期胚胎的发育以及胚胎干细胞的命运决定的，还有很多尚未解决的问题。我们的前期研究发现，着床前胚胎对应的naive状态的多能干细胞与着床后胚胎对应的primed状态细胞在代谢和表观遗传修饰上具有显著差异。尤其一碳代谢通路能通过影响重要代谢中间产物比如SAM影响组蛋白甲基化和核苷酸的代谢，进而影响细胞的命运决定和自我更新。在此基础上，我们将系统研究以下三个问题：（1）在体内发育的胚胎的代谢重塑是如何进行的；（2）上游的多能性因子和发育因子如LIN28, ESRRB是如何调控代谢网络的；（3）重要代谢通路是如何通过影响表观遗传修饰影响基因表达和细胞命运的。这将使我们更好的理解早期胚胎发育的过程。

The mammalian early embryo development is accompanied with cell fate decision and cell division/proliferation. Cell fate changes are determined by the underlying genetic and epigenetic regulation, and cell division/proliferation is dependent on cellular metabolic regulations. How does epigenetic regulation and metabolic regulation are coordinated with each other to promote embryo development, still has many unanswered questions. Our previous research has identified significant difference of epigenetic modification and metabolic regulation between pre-implantation naive pluripotent stem cells and post-implantation primed stem cells. Particularly, the one-carbon metabolism pathway can influence histone methylation as well as nucleotide synthesis through key intermediate metabolites such as SAM (S-Adenosyl-Methionine), thereby regulating cell fate decision and stem cell self-renewal. Based on the previous findings, we aim to carry on further in-depth studies to solve the following questions: (1) how is metabolic network reprogrammed during in vivo early embryogenesis; (2) how does the upstream pluripotent factors regulate metabolic reprogramming; and (3) what are the mechanisms that metabolic pathways can influence epigenetics modifications and thus regulate gene regulation and cell fate decision. Answering these questions will help us to better understand the key events and mechanisms during mammalian early embryo development.