调控损伤微环境中牙髓干细胞的分化进程是牙髓自我修复的关键，该进程受转录因子、表观遗传因子和信号网络的协同作用。我们前期研究发现多能转录因子Oct4对牙髓干细胞的损伤应答具调节作用，能促进细胞增殖和分化，但具体机制不明。T-UCR是转录自基因组超级保守区域的特殊长链非编码RNA，具有重要的遗传学效应。我们前期实验证实牙髓细胞中Oct4表达受T-UCR调控，据此推测牙髓干细胞中Oct4也受T-UCR的表观遗传调控，进而影响干细胞增殖和分化关键因子的表达，介导牙髓损伤修复。本项目拟采用芯片筛选人牙髓干细胞中Oct4相关T-UCR；构建T-UCR过表达和干扰质粒，明确其与Oct4的作用关系及对下游转录因子的调控机制；结合体内成牙本质实验，验证Oct4相关T-UCR修饰的牙髓干细胞诱导损伤牙髓修复再生的能力，以从表观遗传和转录调控角度揭示牙髓干细胞的损伤应答机制，为促进牙髓损伤修复的临床实践提供参考

Regulation of dental pulp stem cell differentiation process, which has been a synergy of transcription factors, epigenetic factors and signaling networks, is crucial for the self-repair of dental pulp in injury microenvironment. Our previous study revealed that the pluripotent transcription factor Oct4 played a regulatory role in the injury response of dental pulp stem cells,promoting cell proliferation and differentiation. However, the specific mechanism remains unknown. As a member of long non-coding RNA family, T-UCR is transcribed from the genome ultraconserved regions, which owns the important genetic effect. Our preliminary experiments confirmed that Oct4 expression in dental pulp cells was regulated by T-UCR. Accordingly, we hypothesize that, in dental pulp stem cells, Oct4 is also epigenetically regulated by T-UCR, thereby affects stem cell proliferation and differentiation and mediates dental pulp repair. This project will firstly screen Oct4 related T-UCRs by using gene chip in human dental pulp stem cells. It will also verify the relationship between T-UCR and Oct4, and the regulatory mechanism of downstream transcription factors based on the T-UCR overexpression and silencing model. Finally, combined with dentinogenesis experiment in vivo, it will demonstrate the capacity of dental pulp repair and regeneration induced by T-UCR modified dental pulp stem cells. This project will reveal the injury response mechanism of dental pulp stem cells from epigenetic and transcriptional regulation perspectives and provide a reference for clinical practice to promote the dental pulp repair and regeneration.