Glis1调控小鼠多能胚胎干细胞重编程为全能性二细胞样细胞的机理研究

代谢重塑在细胞命运决定中具有重要作用。近年来发现在小鼠多能胚胎干细胞重编程为全能性二细胞样细胞的过程中细胞代谢也发生了重塑，然而代谢重塑的规律和作用机理仍不清楚。前期工作我们发现转录因子Glis1调控糖酵解代谢重塑促进多能性获得（Nature Metabolism 2020），近期工作发现在多能性维持中Glis1还能使小鼠多能胚胎干细胞重编程为全能性二细胞样细胞。我们推测Glis1在二细胞样细胞获得中具有重要作用。本项目拟在此基础上进行如下研究：1）确定Glis1对二细胞样细胞获得过程的调控作用；2）揭示Glis1在二细胞样细胞获得过程中对代谢的调控；3）利用代谢探针 “SoNar” 等技术阐明Glis1通过代谢重塑促进二细胞样细胞获得的分子机理。本研究将阐明Glis1调控全能性细胞获得的代谢重塑规律，并揭示Glis1促进全能性细胞获得的机理，为探索细胞命运转变的代谢调控提供重要参考。

Metabolic remodeling plays an important role in cell fate determination. In recent years, it has been found that cellular metabolism is also remodeled during the process of mouse pluripotent embryonic stem cells reprogramming into totipotent 2C-like cells, however the patterns and mechanisms of metabolic remodeling are still unclear. We previously found that Glis1 regulated glycolytic metabolic remodeling and promoted pluripotency acquisition (Nature Metabolism 2020). Recently, we found that Glis1 can also reprogram mouse pluripotent embryonic stem cells into totipotency 2C-like cells. We hypothesized that Glis1 plays an important role in totipotency 2C-like cell acquisition. This project intends to further below：1) to confirm the role of Glis1 in totipotency 2C-like cell acquisition; 2) to uncover the regulation of Glis1 on metabolism pathway in totipotency 2C-like cell acquisition; 3) to demonstrate the molecular mechanisms of metabolic remodeling promoting totipotency 2C-like cell acquisition by metabolic probe “SoNar” and other technologys. Our study is expected to clarify the metabolic remodeling pattern during cell totipotency acquisition, and reveal its metabolic regulation pathway and the mechanisms of Glis1 promoting totipotency cell acquisition. Our project would provide an important idea for exploring the metabolic regulation for cell fate determination.