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题名	猕猴胚胎干细胞体外定向造血分化以及Notch信号通路在造血分化中调控作用的研究
作者	卢斌
学位类别	博士
答辩日期	2011-11
授予单位	中国科学院研究生院
授予地点	北京
导师	季维智
关键词	胚胎干细胞 造血发生 造血内皮细胞 Notch信号通路
其他题名	Notch signal pathway modulates the hematogenic endothelium from rhesus embryonic stem cells.
学位专业	细胞生物学
中文摘要	造血发生是生命发育中一个重要的过程。早在胚胎发育早期，造血发生就已经开始了，来自这一过程的血细胞不断进入循环系统发挥作用。进过多年的研究，人们对于高等哺乳动物造血发生的过程已经有了一定的了解，但是对于早期胚胎造血发生过程的研究一直不是很清楚。近年来在小鼠中的研究证实了早期造血过程中确实存在hemangioblast细胞，并且在体外分化实验中得到了来自胚胎干细胞的hemangioblast细胞，使得人们对于早期造血发生的研究更加深入。最近关于造血内皮细胞的研究报道再次将人们研究早期造血发生的目光聚集起来，体内及体外的实验同时证实了造血内皮细胞确实存在于造血发生过程中，并且是源自hemangioblast细胞的造血前体细胞。这些实验结果为造血研究者们提供了新的研究方向。我们的实验以猕猴胚胎干细胞为基础，建立了共培养的体外造血分化体系。在确定了分化体系有效，可靠之后，我们在体外分化中得到了hemangioblast细胞和造血内皮细胞。实验结果表明，分化第4天的KDR+细胞具有hemangioblast细胞的全部特性，经鉴定确认为hemangioblast细胞；而分化第8天的KDR++CD31+细胞经鉴定具有造血内皮细胞的特性，确认为造血内皮细胞。我们的实验首次在猕猴胚胎干细胞体外分化中得到了造血内皮细胞，并确定了筛选造血内皮细胞的具体时间和标记，为研究灵长类造血发生中的造血内皮细胞开创了前提条件。另外我们研究了Notch信号通路在造血发生中的作用，我们通过抑制剂对Notch信号通路进行抑制，发现造血发生过程在Notch信号通路被抑制后得到了促进，具体到hemangioblast细胞和造血内皮细胞，抑制Notch信号通路后都同样促进了其造血分化。我们的这个实验结果证实了Notch信号通路在造血发生中的作用，并首次发现了抑制Notch信号通路对于造血内皮细胞的造血分化的促进作用，使得人们对于Notch信号通路和造血内皮细胞的理解更加深入。
英文摘要	Hematopoiesis is a significant development process. As far back as the early stage of embryo development, there is hematopoiesis, which input blood cells constantly into circulatory system. After long-range research, people understand the hematopoiesis of mammal in a certain extent. But hematopoiesis during early stage of embryo is still not very clear. In recent years, the research during mouse confirmed the hemangioblast cells in vivo and in vitro. These results improve the understanding of hematopoiesis. Recently, some reports about hematogenic endothelium focus the attention of researchers again. These report identified hematogenic endothelium during hematopoiesis in vivo and in vitro. And the results show that the hematogenic endothelium comes after hemangioblast cells during development. These discoveries provide new aspect for the hematopoietic researchers. During our research, we established an in vitro hematopoietic differentiation system for rhesus embryonic stem cells. Our system base on co-culture system and was proved as a credible and effective system. Then, we obtained hemangioblast cells and hematogenic endothelium from our differentiation system. The results indicated that d4 KDR+ cells from the system are the hemangioblast cells. And the d8 KDR++CD31+ cells are the hematogenic endothelium. Our research firstly obtained the hematogenic endothelium from rhesus embryonic stem cells. We also identified the time and the markers for isolation the hematogenic endothelium. In addition, we studied the Notch signal pathway during hematopoiesis. Inhibited the Notch signal pathway with inhibitor, we discovered that hematopoiesis is improved after inhibiting the Notch signal pathway. For the hemangioblast and hematogenic endothelium, their hematopoietic differentiation is also improved by inhibiting. The results from our research confirmed the effect of Notch signal pathway during hematopoiesis. And our research firstly shows that inhibiting Notch signal pathway can improved hematogenic endothelium. These results are helpful for understanding hematopoiesis clearer.
语种	中文
内容类型	学位论文
源URL	[http://159.226.149.26:8080/handle/152453/10164]
专题	昆明动物研究所_生殖与发育生物学
推荐引用方式 GB/T 7714	卢斌. 猕猴胚胎干细胞体外定向造血分化以及Notch信号通路在造血分化中调控作用的研究[D]. 北京. 中国科学院研究生院. 2011.

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