过氧化物酶体增殖激活受体参与调控小鼠胚胎干细胞分化为胰岛素分泌细胞

发布时间：2018-02-11 14:20

本文关键词： 胚胎干细胞胰岛素分泌细胞定向分化胰岛素分泌线粒体发生膜电位维持过氧化物酶体增殖激活受体　出处：《浙江大学》2011年硕士论文　论文类型：学位论文

【摘要】：胚胎干(embryonic stem, ES)细胞来源于胚泡内细胞群,具有自我更新和多分化潜能的全能干细胞,在体外合适环境下可被诱导分化成机体多种细胞,如神经细胞、心肌细胞、肝脏细胞等。在体外其命运主要由自身固有调控和细胞外微环境双重决定。晚期糖尿病细胞移植治疗目前尚在试验阶段,获得具有insulin分泌功能的胰岛B样细胞,可望促进研究进程。ES细胞自发分化产生的胰岛素分泌(insulin-producing, IP)细胞极少,调控微环境可望促进其分化作用。过氧化物酶体增殖因子活化受体(peroxisome proliferator-activated receptors, PPARs)是核受体超家族成员,包括0c、p、1,三个亚型,在控制脂肪的贮藏和能量分解代谢方面起着重要作用。文献报道,胰岛B细胞的胰岛素分泌作用与ATP产生密切相关,线粒体是产生ATP的重要细胞器,而PPARs与线粒体这一能量发生系统关系密切。本课题组前期研究发现,PPARs不同亚型在Es细胞分化为心肌、肝脏等过程中扮演重要角色,尤其是来自内胚层的肝细胞定向分化与PPARβ受体激动密切相关。但迄今未知同样来自内胚层的IP细胞分化过程中,PPARs各亚型扮演着何种角色。本实验通过三步法诱导小鼠ES细胞定向分化为IP细胞,探索分化过程中线粒体发生(mitochondriogenesis)和线粒体膜电位(mitochondria membrane potential,Δψm)变化情况,PPARs各亚型表达情况及其作用,为发现IP细胞分化过程能量发生特征,促胰岛D样细胞再生药物作用新靶点探索和再生医学细胞移植治疗细胞来源等提供实验依据。
[Abstract]:Embryonic stem stem (ESN) cells, derived from a group of cells in the blastocyst, have the potential of self-renewal and multi-differentiation. They can be induced to differentiate into many kinds of cells in vitro, such as nerve cells and cardiomyocytes. Liver cells and so on. Their fate in vitro is mainly determined by their inherent regulation and extracellular microenvironment. At present, the transplantation of advanced diabetic cells is still in the experimental stage, and the pancreatic islet B-like cells with the function of insulin secretion have been obtained. There are very few insulin secretory insulin-producing (IPs) cells, and the regulation of microenvironment can promote the differentiation. Peroxisome proliferator-activated receptor (PPARs) is a member of nuclear receptor superfamily. It is reported that insulin secretion of islet B cells is closely related to the production of ATP, and mitochondria are important organelles for the production of ATP. However, PPARs is closely related to mitochondrial energy generation system. Our previous study found that different subtypes of PPARs play an important role in the differentiation of es cells into myocardium and liver. In particular, the directional differentiation of hepatocytes from the endoderm is closely related to the activation of PPAR 尾 receptor. However, it is not known what role each subtype of PPARs plays in the differentiation of IP cells from the endoderm. Mouse es cells differentiated into IP cells. To explore the changes of mitochondrial membrane potentialand mitochondrial membrane potential (螖蠄 m) in the process of differentiation, the expression of PPARs subtypes and their roles in the process of IP cell differentiation were investigated. To explore the new target of promoting D-like cell regeneration of pancreatic islets and to provide experimental basis for cell source of regenerative medical cell transplantation.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R329

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