哺乳动物细胞的第一次谱系分离是早期胚胎发育的关键步骤，它的发生与特异性转录因子Cdx2等的限制性表达有关。在以往的研究中，我们发现小鼠胚胎干细胞（mESCs）在G1期细胞周期蛋白（G1 cyclins）全部缺失后，Cdx2转录水平明显上调，更倾向于向滋养外胚层分化，提示G1 cyclins可能通过调控Cdx2参与了谱系分离。本项目将首先筛选出从受精卵到囊胚过程中的卵裂球间表达异质性的G1期cyclin，观察其与Cdx2表达的时空相关性；然后在分子水平探索相关cyclin如何调控Cdx2，找出CDX2上的应答元件；最后，构建出应答元件缺失的CDX2突变体mESCs和嵌合胚胎，观察其表型，从体内体外方面，分析其分化发育和谱系分离能力，进一步验证G1 cyclins对Cdx2的调控机制，明确G1 cyclins对谱系分离的影响。这将对了解哺乳动物早期发育、再生和肿瘤等疾病都有重要意义。

The first lineage segregation is a critical process to early mammalian development. It is related to the restricted expression of specific transcription factors, such as Cdx2. In previous studies, we found that after depletion of G1 cyclins, mouse embryonic stem cells showed high transcription levels of trophectoderm markers including Cdx2, and had the preference to differentiate into trophectoderm. This indicated that G1 cyclins might play a role in the first lineage segregation via regulating the expression of Cdx2. In this project, first, cyclin(s) with heterogeneity among blastomeres will be selected, and its correlation with Cdx2 in temporal and spatial expression pattern will be investigated. Then, the molecular mechanism of how G1 cyclins regulate Cdx2 will be explored, and CDX2 response elements to cyclins with will be identified. Lastly, to further confirm the involvement of G1 cyclins in first lineage segregation, ES cells and chimeric embryos with Cdx2 mutant lack of response elements to cyclins will be generated, and the phenotypes in pluripotency and differentiation will be analyzed. This project will provide evidence for the novel function of G1 cyclins in first cell fate decision, defining a new link between cell cycle and first lineage segregation in early development of mammals.