唐氏综合征诱导多能干细胞模型的研究进展

Progress of research on induced pluripotent stem cell models for Down syndrome

唐氏综合征(Down syndrome,DS)是人类最常见的染色体遗传病,发病率为1/800~1/600,是由21号染色体重复导致的遗传物质异常疾病,大部分病例为标准型,核型为47,XX(或XY),+21,较少病例为易位型或嵌合体型。唐氏综合征患者主要特征为智能落后、特殊面容和生长发育迟缓,可表现为先天性心脏病、十二指肠狭窄、阿尔茨海默病、白血病、免疫缺陷病等。21号染色体上基因的数量变化导致了唐氏综合征的性状。虽然新的研究表明其与表观遗传学的机制有关,但其分子层面上的致病机制仍未知。伦理因素限制了对唐氏综合征和人类其他三体疾病患者的研究,且目前常用的小鼠模型并不能完全模拟唐氏综合征的基本性状。将来自唐氏综合征患胎细胞或组织诱导为诱导多能干细胞(induced pluripotent stem cells,iPSCs),可获得个体化、含有相同遗传物质的细胞模型,这为研究唐氏综合征发病机制和定制细胞治疗及基因治疗方案提供了一种有价值的材料。

With an incidence of 1/800-1/600,Down syndrome(DS)is the most common chromosomal disorder in humans.Whilst most DS patients has trisomy 21,a small proportion may carry translocations or mosaicisms involving chromosome 21.The main characteristics of DS include mental retardation,peculiar facies,growth retardation,congenital heart disease,duodenal stenosis,Alzheimer’s disease,leukemia,and immunodeficiency,which may be due to increased dosage of critical genes.Recent studies also showed that epigenetic changes may also occur in DS.For research on patients with DS or other trisomies have been restricted by ethical considerations,and commonly used mouse models cannot fully replicate the characteristic features of DS,pluripotent stem cells induced from fetal samples or biopsy tissues from DS patients may generate models with the same genetic content,which may provide idea materials for studying the pathogenesis of DS and customized cell and/or gene therapies.