NCOA3在人胚胎干细胞多能性维持中的作用及其调节机制

Nuclear receptor coactivators have important roles in cell proliferation, differentiation and tumor development, but their functions in embryonic stem cells are rarely reported. In our previous studies, we found for the first time that nuclear receptor coactivator Ncoa3 plays a key role in pluripotency maintenance in mouse embryonic stem cells. Since the four key functional domains of Ncoa3 are highly conserved in human, we speculated that NCOA3 may be involved in pluripotency maintenance of human embryonic stem cells and naïve cells. Therefore we hypothesized that NCOA3 can maintain pluripotency of human embryonic stem cells and naïve cells. We will verify our hypothesis by knocking-down NCOA3 in human embryonic stem cells/naïve cells to evaluate its function in pluripotency maintenance, performing ChIP-Seq and microarray analysis to clarify the mechanism, and also investigating at post-translational level. We will also examine NCOA3’s functions in reprogramming and in transition from primed to naïve stem cells. Through the study of this subject, we expect to find functions of NCOA3 in human embryonic stem cells, naïve stem cells and reprogramming, and also clarify the mechanism so as to enrich the regulatory network and promote clinical application.

核受体辅助因子在细胞增殖、分化和肿瘤发生等生物学过程中有重要作用，但是其在胚胎干细胞中的功能却很少有报道。我们前期发现，核受体辅助因子Ncoa3在小鼠胚胎干细胞多能性维持中起关键作用。Ncoa3的四种关键功能结构域高度保守，这提示NCOA3可能参与人胚胎干细胞多能性维持。为此我们提出假说：NCOA3对维持人胚胎干细胞的多能性起关键作用。本课题拟在人胚胎干细胞中干扰NCOA3，检测多能性相关指标，进行ChIP-Seq和microarray分析，并从翻译后修饰水平阐明NCOA3对多能性的作用及调控机制。同时探讨NCOA3对重编程的影响及在primed和naive干细胞转化中的作用。通过本课题的研究，有望证明NCOA3在人胚胎干细胞、naïve细胞和体细胞重编程中的功能，并阐明其作用机制，从而丰富多能性调控网络，推进干细胞的临床应用。