诱导多能干细胞（IPSC）技术的发明表明转录因子在细胞重编程方面发挥关键作用，然而转录因子协同调控细胞命运的分子机理仍有待阐明。本项目前期建立了一套新型高效的诱导多能干细胞因子体系，并发现其中关键转录因子GLIS1,ESRRB在诱导多能干细胞过程中具有显著的剂量效应，该发现提示转录因子调控细胞命运的存在更加精细的模型。本项目拟结合时间序列ATAC-seq,ChIP-seq以及IP-MS等染色质和蛋白质研究技术，系统研究GLIS1和ESRRB在不同剂量条件下的表观遗传动态变化谱，基因表达谱和蛋白质互作谱，进而建立转录因子剂量效应通过表观遗传机器影响体细胞重编程的分子作用模型。该研究将从定量角度揭示转录因子影响细胞重编程的新机制。

The invention of induced pluripotent stem cell (IPSC) indicated that transcription factors play a key role in somatic cell reprogramming. However, the detailed molecular mechanisms remain to be elucidated. Previously, we formulated a new set of transcriptional factor cocktails, in which, GLIS1 and ESRRB had significant dose effect. Those result offer us an ideal model to investigate the mechanism of cell fate transition quantitatively. In this project, by utilizing the chromatin and protein machinery analysis technologies, such as ATAC-seq, ChIP-seq and IP-MS, we will investigate the dynamics of gene expression, epigenetic modification and protein-protein interaction responded to the dosage effect, and then find the correlations between them. Finally, we will set up a model by which the dose effect of transcription factors function through epigenetic machinery to modulate the somatic cell reprogramming. This study will reveal the new mechanisms by which transcription factors affect cellular reprogramming quantitatively.