运用iPS技术来建立非整倍体疾病模型

发布时间：2018-06-15 02:38

本文选题：Turner疾病 + 8三体　；参考：《中国科学技术大学》2011年硕士论文

【摘要】：人类很多种疾病都拥有一个共同的早期发育过程,有的疾病症状在儿童时期表现出来,有的疾病的症状是在成年中表现出来。非整倍体疾病是一大类疾病,这些疾病对个人,家庭以及社会带来了很大的影响。这一类疾病主要是在染色体水平上发生了变化,有的疾病是多了一条三色体,有的疾病是少了一条染色体,有的疾病是镶嵌性的,也就是个体的细胞中有的是正常的核型,也有异常的核型。非整倍体是一类早期发育相关的疾病,对患有这种疾病的个体,无论在出生前或者是出生后,都会带来灾难性的后果,重者导致个体在很早的时期就会死亡,甚至都不会有个体的产生,轻者会在以后的生活中有各种各样的临床症状表现。到底是什么原因导致了这些非整倍体疾病的个体会发生胎儿的流产呢,研究这些非整倍体疾病的基因表达水平是非常重要的一个方面,因为我们可以通过了解基因表达水平的差异,来判断是什么基因导致了这些疾病个体发育的异常,同样也为以后的临床治疗提供理论基础。我们本实验的目的,通过利用iPS技术来建立这些非整倍体疾病模型的细胞系,来增加我们对这些非整倍体疾病的了解。我们通过体外重编程诱导了3个Turner病人的iPS细胞系,一个8三体的iPS细胞系,一个13三体的iPS细胞系,一个部分11和22三体的iPS细胞系.重编程的非整倍体疾病iPS细胞系,维持了供体细胞的异常核型,通过一系列的多能性鉴定,显示这些非整倍体疾病的iPS在功能上和胚胎干细胞很相似,可以自我更新,同样也具有分化成三个胚层的能力。对于Turner疾病的iPSCs,我们进行了更深入研究,包括整个基因组转录水平的比较,体外定向分化成三个胚层能力的研究,以及通过胚胎小体来研究胎盘基因表达的差异。通过这些实验得到的结果分析,我们可以得到一个初步的结论,对于Turner疾病的个体,在早期的胚胎发育过程中,是由于胎盘发育的异常导致的胎儿流产,并不是在特定组织分化能力上出现的问题。
[Abstract]:Many human diseases share a common early development process, some of which are manifested in childhood and others in adulthood. Aneuploidy is a class of diseases that have a great impact on individuals, families and society. This kind of disease mainly changes at the chromosome level, some diseases are more than one trichrome, some diseases are missing one chromosome, some diseases are mosaic, that is, some of the individual cells have normal karyotype. There are also abnormal karyotypes. Aneuploidy is a kind of disease associated with early development that can have disastrous consequences for individuals with this disease, both before and after birth, causing individuals to die at an early age. There will not even be individuals, and the lighter will have a variety of clinical symptoms in later life. What causes these aneuploidy diseases to cause fetal abortion, so it's important to study the level of gene expression in these aneuploidy diseases. By understanding the differences in gene expression levels, we can determine which genes cause the abnormal development of these diseases, and also provide a theoretical basis for future clinical treatment. Our aim of this study is to establish the cell lines of these aneuploidy disease models by using iPS technique to increase our understanding of these aneuploidy diseases. We induced 3 Turner patient iPS cell lines, an 8 trisomy iPS cell line, a 13 trisomy iPS cell line and a partial 11 and 22 trisomy iPS cell line by in vitro reprogramming. The reprogrammed iPS cell lines with aneuploidy maintain the abnormal karyotype of donor cells, and a series of pluripotent identification shows that the iPS of these aneuploidy diseases are functionally similar to embryonic stem cells and can be self-renewing. It also has the ability to differentiate into three layers. For Turner's disease iPSCs, we have carried out further research, including the comparison of the transcription level of the whole genome, the ability to differentiate into three embryo layers in vitro, and the difference of placental gene expression through embryosome. By analyzing the results of these experiments, we can draw a preliminary conclusion that in individuals with Turner's disease, in the early stages of embryonic development, it is due to abnormal placental development that causes the abortion of the fetus. It is not a question of the ability of a particular organization to differentiate.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R-332

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