| 题名 | RhoGDI alpha 对兔滋养层干细胞增殖、迁移和分化的调控作用研究 |
| 作者 | 张锦娟 |
| 学位类别 | 硕士 |
| 答辩日期 | 2014-05 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 郑萍 |
| 关键词 | RhoGDI 兔滋养层干细胞 胎盘发育 迁移 细胞凋亡 TSC 自我更新 细胞分化 |
| 其他题名 | The function research of RhoGDI alpha in rabbit TS cell proliferation, migration and differentiation |
| 学位专业 | 细胞生物学 |
| 中文摘要 | 胚胎发育伴随着细胞的一系列连续分化，哺乳动物胚胎的最早期分化产生了滋养层，滋养层在之后的发育中只参与到胎盘的形成，是胎盘的重要组成成分。滋养层干细胞是滋养层中能够进行自我更新，并且能够在一定的条件下分化为滋养层谱系不同细胞类型的成体干细胞，它存在于早期囊胚的滋养外胚层以及胎盘形成时期的细胞滋养层中，补充更新滋养层细胞谱系。滋养层的发育异常与不孕、习惯性流产以及新生儿疾病的发生有重要关联。习惯性流产以及葡萄胎中滋养层常出现凋亡以及炎症相关基因的异常表达，此外妊娠并发症的发生也与胎盘转录本以及代谢的变化有关。滋养层干细胞的成功分离与建系为人们在体外研究滋养层的生长发育提供了有利条件。在本文中我们用兔胚胎干细胞定向分化获得的滋养层干细胞研究RhoGDIα在滋养层干细胞自我更新和分化中的作用。RhoGDI是RhoGTPase的结合蛋白，抑制RhoGTPase的活化，阻止RhoGTPase下游效应因子的激活。在我们的前期研究中，我们发现在发生凋亡的滋养层干细胞中，RhoGDIα的表达上调，提示我们RhoGDIα可能在滋养层干细胞的自我更新和分化中起着作用。通过本研究我们证实了RhoGDIα确实参与了滋养层干细胞的自我更新，并且对滋养层的凋亡起着促进作用。此外，我们还发现对RhoGDIα的敲减，有利于滋养层干细胞的自我更新，促进了滋养层干细胞的迁移，而且RhoGDIα对滋养层干细胞迁移能力的改变并不是通过促进滋养层细胞的分化来实现的，RhoGDIα的敲减并未引起滋养层细胞的分化。我们的研究证实了RhoGDI对滋养层干细胞增殖凋亡和迁移的调控，而对滋养层的分化并没有明显影响。 |
| 英文摘要 | Embryonic development is accompanied by a series of cell differentiation, by which highly specialised cell types are developed from a single undifferentiated, fertilised egg. One of the earliest lineages to form in mamalian conceptus is the trophoblast, which only contributes to extraembryonic constructs and is the essential component of the placenta. Trophoblast stem cells derived from early trophectoderm and later placental villous tissue were pluripotent cells which can undergo selfrenewal in supporting medium and give rise to trophoblast lineages in differentiation conditions. Abnormal development of trophoblast is related to primary infertility, recurrent abortion and newborn infant diseases. Aberrant placental expression of apoptosis and inflammation-related genes in early pregnancy was found in recurrent miscarriage and hydatidiform mole samples. Altered placental transcription of metabolic regulatory genes has been associated to affected fetal growth and maternal pregnancy complications. The successful establishment of trophoblast stem cell line benefits the in vitro research of trophoblast development. This study aimed to detect RhoGDIα fonction in rabbit trohoblast cells maintenance and differentiation. RhoGDI is the binding protein of RhoGTPase, which inhibits RhoGTPase activation. In our previous work, we found the apoptosis of trophoblast cells was accompanied by RhoGDIα up-regulation, suggesting the possible functions of RhoGDIα in regulating trophoblast stem cell maintenance. In this research, we further reveal that RhoGDIα took part in the regulation of trophoblast stem cell self renewal and its over expression led to apoptosis in trophoblast cells. we also found that knocking down of RhoGDIαpromoted trophoblast stem cells migration without affecting differentiation. Our results verify RhoGDIα has a function in trophoblast stem cell maintenance and migration, but has no obvious influence on trophoblast cell differentiation. |
| 语种 | 中文 |
| 公开日期 | 2014-06-04 |
| 内容类型 | 学位论文 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7884]  |
| 专题 | 昆明动物研究所_哺乳动物胚胎发育 |
| 推荐引用方式 GB/T 7714 | 张锦娟. RhoGDI alpha 对兔滋养层干细胞增殖、迁移和分化的调控作用研究[D]. 北京. 中国科学院研究生院. 2014. |
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