18-三体综合征是仅次于21-三体综合症的第二种常见染色体三体征。由于缺乏有效的疾病模型，其致病机制尚无法深入研究。前期研究中我们建立了18-三体诱导多能干细胞系（18T-iPSCs），发现18-三体iPS细胞在培养过程中容易发生自发分化，且多余的染色体在传代数代后丢失。我们拟通过定向诱导分化，观察比较18T-iPSCs向各个胚层分化的能力，同时进行功能学分析，明确18-三体对各胚层细胞的功能影响。通过RNA sequencing和生物信息学分析，寻找18T-iPSCs中异常表达的基因，再利用过表达和敲低等实验技术，对这些基因是否能造成18T-iPSCs异常分化进行功能验证。通过我们的研究，将有助于寻找18-三体综合征致病内在的分子机制，从而为预防或者治疗这一疾病提供理论依据。

The trisomy 18 syndrome, is the second most common autosomal trisomy syndrome besides trisomy 21 syndrome. However, the molecular mechanisms remain unclear. Previous we successfully generated trisomy 18 induced pluripotent stem cells (18T-iPSCs) derived from human amniotic fluid cells with trisomy 18. We found that 18T-iPSCs were prone to lost the extra 18 chromosome and differentiate spontaneously. 18T-iPSCs will be induced to differentiate towards each three germlines, the efficiencies of differentiation will be compared to diploid iPSCs. Functional studies will be also performed to investigate the effect of trisomy 18 on each lineage cells. By RNA sequencing and bioinformation analysis, we expect to find some genes aberrantly expressed in 18T-iPSCs. We will further verify if these genes play roles in the differentiation of 18T-iPSCs via gain-of-function and loss-of-function studies. Our research will help to elucidate the molecular mechanisms of the trisomy 18 syndrome, and lay a foundation to prevent or treat this disease.