胚胎干细胞（ESCs）具有无限的自我增殖和分化多能性的特点，统称为干性。ESCs通过表达特殊转录因子，以及维持染色质的“开放”模式,从而保持其细胞命运决定的可塑性。目前，对调节ESCs染色质状态的机制尚未阐明。我们前期研究筛选出一个在ESCs中特异性高表达的染色质结合蛋白Top2a，并首次确定其具有维持ESCs干性的新功能。为全面理解Top2a调节干性的分子机制，本研究拟通过ChIP-seq结合RNA-seq的方法，解析干性维持中Top2a的转录调控网络；同时，我们还将在蛋白质组水平筛选与Top2a互作的蛋白因子，并研究该复合体在干性调控中的作用机制；在充分阐明Top2a调节ESCs干性的分子机制的基础上，我们将进一步探索Top2a在促进诱导性多能干细胞（iPS）生成和调控肿瘤干细胞分化过程中的作用，并尝试通过抑制Top2a表达从而诱导肿瘤干细胞的分化，有望为癌症治疗提供潜在的治疗新方案。

Embryonic stem cells (ESCs) exhibit stemness, which is defined by the ability to self-renew indefinitely and differentiate into all the cell types from three germ layers. ESCs can keep the plasticity by expressing particular transcription factors and maintaining open chromatin. Nowadays, molecular mechanisms of regulation of chromatin status in ESCs remains largely unclear. Our previous work identified a chromatin-binding protein Top2a, which is highly expressed in ESCs, as a novel regulator of stemness. To obtain a comprehensive understanding of Top2a acting in stemness, we propose to first elucidate the regulatory network of Top2a in keeping stemness by utilizing ChIP-seq combined with RNA-seq techniques. Meanwhile, we propose to screen out Top2a-interacting proteins using proteomic approaches, and explore roles of the Top2a complex in regulation of stemness. Based upon this, we will continue to investigate if and how Top2a regulates reprogramming efficiency and differentiation of cancer stem cells. Furthermore, our attempt on inducing differentiation of cancer stem cells by silencing Top2a would potentially provide new strategies to cancer therapy.