小鼠早期胚胎发育过程中第一次细胞命运决定很大程度上由一些关键的转录因子来调控。最近开发的绘制转录因子图谱的方法CUT&RUN能够利用最少1000个细胞来绘制隔绝子CTCF的结合位点图谱。然而，由于小鼠早期胚胎细胞数量的稀缺性，要求更为敏感的技术来研究细胞命运决定过程中的转录调控机制。本项目拟通过：（1）改进现有CUT&RUN技术以绘制小鼠早期胚胎发育过程中，在第一次细胞命运决定中可能起关键作用的转录因子图谱；（2）结合相应发育阶段的基因表达数据，鉴定第一次细胞命运决定中真正发挥作用的关键转录因子；（3）进一步结合多组学数据及功能性实验，探讨细胞命运决定调控的相关分子机制。本项目将全面阐述小鼠早期胚胎发育过程中第一次细胞命运决定的关键转录调控机制，为生殖医学和相关疾病的治疗提供理论基础。

Cell fate decisions in the early embryonic development of mouse are orchestrated in large part by the concerted actions of transcription factors. A recently described method for genome-scale profiling of transcription factors, CUT&RUN, has been successfully used to map the insulator protein CTCF from as few as 1,000 cells. However, this method is still insufficiently sensitive to allow mapping in individual pre-implantation embryos. A more sensitive methods for characterizing their regulation and functions are necessary to better understand. In this study, we propose to improve the performance of CUT&RUN and overcome the technology barriers in investigating the profiles of transcriptional regulatory factors in early embryo. Using this updated method, we could generate the binding site profiles of potential core transcription factors in cell fate decisions related periods. By integrating gene expression data, we could identify the key transcription regulators in the determine of cell fate. Furthermore, we will illustrate the molecular mechanism of cell fate decisions by combing multi-genomics analysis and functional experimental validation. Our study will comprehensively illustrate the transcriptional regulation network of the first cell fate decisions during the mouse early embryonic development, and eventually provides the theoretical foundation for the treatment of reproductive medicine and other related diseases.