人胚胎干细胞（human embryonic stem cell, hESC）具有无限自我更新和分化为机体内任何种类细胞的能力，有广泛的应用前景。阐明其特性维持的分子机制对hESC的应用具有重要意义。我们在前期研究中发现了若干个对hESC自我更新所必需的重要基因，包括本项目拟研究的C20ORF14。已知该基因参与转录后RNA选择性剪接的调控。但它在hESC中的作用尚无报道。我们的初步研究结果显示，C20ORF14可能在转录后层面调控hESC的基因表达，进而影响hESC基因组稳定性和自我更新。我们拟在本项目中，确认C20ORF14与hESC基因组稳定性的关系；发现C20ORF14维持hESC基因组稳定性的关键效应分子；阐明C20ORF14调控选择性剪接的分子机制。通过本项目的实施，揭示RNA选择性剪接事件对基因组稳定性和细胞命运决定的调控机制，为提高hESC体外扩增和定向分化效率养提供指导。

Human embryonic stem cells (hESCs) possess capacities of indefinite self-renewal and differentiation into any cell types of an organism, holding great application potential. Understanding the molecular mechanisms controlling their unique properties is important for efficient amplification of hESCs. Previously, we identified a list of important genes required for hESC self-renewal. Among these genes, C20ORF14 is selected for this program. C20ORF14 is known to implicate in the regulation of posttranscriptional RNA alternative splicing events. However, its function in hESC has not been reported. Our preliminary results indicate that C20ORF14 possibly regulates gene expression via an alternative splicing mechanism to affect genome stability and self-renewal in hESC. In this program, we plan to further verify the relationship of C20ORF14 with hESC genome stability; identify key effectors mediating the function of C20ORF14 for the maintenance of genome stability; elucidate the underlying mechanisms by which C20ORF14 controls alternative splicing events. Through completing this program, we seek to understand the molecular basis of hESC genome stability maintenance and cell fate determination at an alternative splicing level and to provide guides for efficient amplification and directed differentiation of hESCs.