胚胎干细胞（ESCs）在体外能够无限地自我更新，同时保持着分化成各种组织细胞的能力，具有重大的社会和经济价值。前期我们发现转录因子Tfcp2l1不仅可以促进小鼠ESCs的自我更新，还可以重编程小鼠上胚层干细胞（mEpiSCs）回到ESCs状态。但其作用的分子机制还不清楚。本课题拟应用蛋白质和染色质免疫共沉淀技术，结合基因的过表达和干扰等方法，拟鉴定Tfcp2l1促进小鼠ESCs自我更新的核内相互作用蛋白及下游关键靶基因。因mEpiSCs和目前所建立的人ESCs具有相似的生物学特性，所以我们也将在人ESCs中单独上调Tfcp2l1的表达或共表达Tfcp2l1与其他多能性基因，明确其是否可以促进人ESCs原始（Naïve）多能性状态的产生。本项目的研究结果不仅将拓展目前人们对ESCs自我更新调控网络的认识，还将为分离和培养其他物种的ESCs及安全应用ESCs提供线索。此项研究国内外尚无报道。

Embryonic stem cells (ESCs) can be maintained in culture indefinitely while retaining the capacity to generate any type of cell in the body, and therefore hold great promise for tissue repair and regeneration.We previously reported that Tfcp2l1 can not only promote mouse ESC self-renewal, but also can reprogram post-implantation mouse epiblast stem cells (mEpiSCs) to naive pluripotent ESCs. However, the molecular mechanism of the self-renewal-promoting effect of Tfcp2l1 in ESCs remains unclear. In our study, We will identify the interacting proteins and the key target of Tfcp2l1 via using Co-IP and ChIP methods, combined with gene gain and loss of function technology. Notably, human ESCs are similar to mEpiSCs in growth requirements, morphology, clonogenicity, and gene expression patterns, we therefore will investigate whether transfection of human ESCs with Tfcp2l1 in absence or presence of other exogenous pluripotecy genes, like Oct4 or Klf4, can induce naive pluripotency. Our project will not only provide an expanded understanding of the current model of ground-state pluripotency, but also will facilitate the development of new culture conditions for the derivation of authentic ESCs from other species.