胎儿生长受限相关lncRNA在干细胞定向神经分化中的作用与机制

不良宫内环境常会通过表观遗传改变诱发胎儿生长受限（FGR），继而增加成年期精神类疾病患病风险。长链非编码RNA（lncRNA）作为表观遗传调控新成员，在胚胎发育和细胞命运决定中具有重要作用，但FGR相关lncRNA及其在干细胞命运决定中的作用和机制尚不明确。本项目将利用FGR小鼠模型与非编码RNA研究特长，结合高通量测序和生物信息分析筛查调控FGR和神经分化的特异性lncRNA，明确特定FGR-lncRNA在干细胞定向神经分化中的功能，通过RIP和报告基因实验等阐明FGR-lncRNA调控干细胞定向神经分化的作用机制。在此基础上，再将关键lncRNA介入FGR小鼠模型，分析关键lncRNA对FGR子代小鼠神经发育和精神行为异常的干预效果。本项目的完成，将全面阐释FGR-lncRNA介导干细胞定向神经分化的表观遗传特异性网络，为深入探究干预FGR疾病的非编码RNA靶标提供参考依据和理论基础。

Adverse intrauterine environment often induces fetal growth restriction (FGR) through epigenetic changes, which in turn increases the risk of mental disorders in adulthood. Long noncoding RNA (lncRNA), as a new member of epigenetic regulation, plays an important role in embryonic development and cell fate determination. However, the role and mechanism of FGR related lncRNA in determining the fate of stem cells remains unclear. Based on our research specialty in FGR mouse model and noncoding RNA, this project will combine high-throughput sequencing with bioinformatics analysis to screen the specific lncRNA that regulates FGR and neural differentiation, and clarify the specific function of FGR-lncRNA in directed neural differentiation of stem cells. The functional mechanism of FGR-lncRNA in the directed neural differentiation of stem cells will be elucidated by RIP and reporter gene experiments. On this basis, through FGR mouse model and mental behavior detection, the key lncRNA molecules will be introduced into FGR mouse model to analyze its intervention effect on abnormal neural development and mental behaviors of FGR mice. The completion of this project will fully explain the FGR-lncRNA-mediated epigenetic specific network during neural differentiation of stem cells, and provide reference and theoretical basis for clinical intervention of FGR diseases with noncoding RNA.