脂肪细胞分化对于机体物质代谢和能量平衡具有重要意义。RNA结合蛋白介导的基因转录后调控在干细胞分化中发挥重要功能。我们在前期研究中首次发现RNA结合蛋白—NOVA1在脂肪间充质干细胞成脂分化过程中有重要作用，基因表达谱芯片和CLIP-Seq研究发现NOVA1调控大量未折叠蛋白反应(UPR)和PPARγ通路相关基因。为明确NOVA1如何通过UPR和PPARγ通路相关基因的转录后调控进而影响脂肪细胞分化，本课题将首先分析NOVA1对UPR和PPARγ通路相关基因的剪接和稳定性调控，继而阐明其对UPR应答和PPARγ通路活化程度的影响以及其在成脂分化中的作用，最后应用NOVA1敲除小鼠验证NOVA1对脂肪细胞分化和脂代谢的影响，以及UPR和PPARγ通路基因的转录后调控在脂肪细胞分化与脂代谢中的作用。本研究将对脂肪细胞分化调控机制研究取得重要突破，并为脂肪代谢异常疾病的治疗提供参考。

The differentiation of adipose-derived stem cells is critically important in the material metabolism and energy balance of the body. RNA binding proteins mediated gene post-transcriptional regulation are important in the differentiation of stem cells. We found for the first time that NOVA1, a RNA binding protein, plays critical roles in the adipogenesis of adipose-derived stem cells. Gene expression analysis and CLIP-Seq analysis revealed that NOVA1 regulate genes involved in ER stress and adipose synthesis. To uncover the post transcriptional mechanism of NOVA1 in the regulation of unfolded protein response (UPR) and PPARγ signal which regulates adipogenesis, we will firstly study the regulation of NOVA1 on the splicing and stability of genes related to UPR and PPARγ signal. Then we will study the post transcriptional regulation on the activation of UPR and PPARγ signal pathway and their roles in adipogenesis and lipid metabolism. Finally, we will verify the regulation of NOVA1 in UPR and adipogenesis in NOVA1 knock out mouse. This project would make great contribution to the differentiation of stem cells, which would shed light on treatment of metabolism abnormality.