Naïve胚胎干细胞（ESCs）和primed 上胚层干细胞（EpiSCs）分别是从小鼠植入前囊胚和植入后早期上胚层分离得到的多能干细胞，但是这两种干细胞的特性以及相互之间转化的调控机制至今尚不清楚。我们前期建立了小鼠扩增性潜能多能干细胞（Nature，2017），在此基础上我们应用CRISPR-Cas9技术筛选又获得了重编程EpiSC的新基因Sall1。本课题将对Sall1重编程primed EpiSCs、小鼠和人成纤维细胞进行功能鉴定；观察Sall1过表达、敲除对ESCs转化为EpiSCs和三胚层分化的影响；分析Sall1与干性基因Nanog在重编程以及naïve ESC向primed EpiSCs转化的协同作用；并利用RNA-Seq检测相关下游基因及其潜在的分子机制。最终为深入了解早期胚胎植入和细胞分化的机制提供关键的参考依据，研究结果具有重要的生物学意义和应用价值。

Naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs) are derived from epiblast of blastocyst (E3.5-4.5) and post-implantation embryo (E5.5-7.5) respectively. However, the characteristics of these two pluripotent stem cells and the molecular mechanism of the control the transition between them are still not clear. Recently, we’ve established mouse expanded potential stem cells (Nature, 2017); moreover, we designed whole genome gRNA library combing with dead Cas9 (dCas9) linked with DNA activation domain to screen genes in EpiSCs reprogramming and found a new candidate gene Sall1. In this project, at first, we will validate Sall1’s function in EpiSCs and somatic cell reprogramming; investigate its roles in the conversion of naïve ESCs to primed EpiSCs, the three lineage differentiation of ESC by overexpression or knock-out Sall1 in ESCs; then, examine the synergistic effects of Sall1 and its partner Nanog (a key naïve pluripotent factor) in reprogramming and conversion of naïve ESCs to primed EpiSCs; finally, identify the down-stream target genes of Sall1 and Nanog by RNA-Seq and investigate the regulation of target gene expression. The data generated in this project will provide new insights into early embryo implantation and lineage commitment of mouse and human and the mechanism of reprogramming, which will not only advance the research in biology but facilitate future application in biomedicine as well.