细胞周期结构影响干细胞多能性建立的机制研究

多能性干细胞具有与体细胞不同的细胞周期分子调控机制和细胞周期结构，已知在使用诱导多能干细胞技术进行多能性重建的过程中细胞周期结构会发生转变，但是导致这种细胞周期结构改变的分子机制尚不明确。项目前期研究发现在更加快速的重编程系统中，细胞周期结构转变能够先于多能性建立，因此我们提出细胞周期结构转变能够更快的帮助细胞建立多能性状态的假设。本项目拟利用传统OSK和更加快速的OvSvK重编程细胞模型，围绕细胞周期结构转变的原因及其对多能性建立的作用开展研究。通过结合单细胞测序，流式分析分选以及ChIP-seq、ATAC-seq等技术，旨在发现体细胞重编程过程中导致细胞周期结构改变的分子机制，以及细胞周期结构改变影响干细胞多能性建立的分子机制，进而为理解细胞周期影响细胞命运变化的基本生物学规律、有效的实现功能细胞的获得提供理论和应用的指导。

Pluripotent stem cells have distinct regulatory mechanisms and patterns of cell cycle comparing to somatic cells. Cell cycle patterns are known to change during somatic reprogramming and pluripotency reset. However, the molecular mechanism of cell cycle alteration is still unclear. Our preliminary data showed that in a high-efficiency reprogramming system, cell cycle transitions were established before the setup of pluripotency, leading to the hypothesis that cell cycle changes facilitate pluripotency establishment. In this project, we aim to investigate the causes of cell cycle changes and their role in the pluripotency establishment by comparing the traditional OSK and the high-efficiency OvSvK reprogramming systems. Combining single-cell RNA-seq, FACS, ChIP-seq, ATAC-seq, we proposed to reveal the mechanism of cell cycle alteration during somatic reprogramming and its impact on the establishment of pluripotency. Through this project, we could get a better understanding of how the cell cycle affects the cell fates and provide new theoretical and practical guidance for the acquisition of functional cells.