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Basic Study for Regenerative Medicine : Differentiate of Embryonic Stem Cells to Hepatocytes and Expressions of Cytochrome P450 in the Differentiating Cells

再生医学基础研究：胚胎干细胞向肝细胞的分化及分化细胞中细胞色素P450的表达

基本信息

批准号：
15390047
负责人：
OHMORI Shigeru
金额：
$ 9.47万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To differentiate mouse embryonic stem (ES) cells to hepatocytes, embryoid bodies were cultured for 36 days. Hepatocyte differentiation markers were expressed in the cells differentiated from ES cells. The expression pattern of cytochrome P450 (CYP) genes in the cells could be grouped into four different categories, such as highly expressed at early to mid stage, only expressed at late stage ; expressed throughout at all stages and not detectable at any stages. Aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator and glucocorticoid receptor were detected in the cells cultured throughout the time course. Pregnane X receptor was detected only the cells cultured for more than 24 days. The alpha-fetoprotein and albumin were co-expressed with CYP3A2 and CYP1A1, respectively. Monkey ES cells were also differentiated into hepatocytes in vitro. The cells expressed alpha-fetoprotein, albumin, CYP3A8, CYP3A66 and CYP7A1. We have isolated a cDNA clone from the differentiating monkey ES cells and identified a novel CYP isoform, named CYP3A7m. Deduced amino acid sequence of CYP3A7m shows 89, 81, 91 and 72% homology to CYP3A4, CYP3A5, CYP3A7 and CYP3A43, respectively. These results suggested that CYP and transcription factor genes were expressed in hepatocytes differentiated from ES cells and those expression levels and patterns were considerably changed in individual enzymes during the course of the differentiation.

为了将小鼠胚胎干（ES）细胞分化为肝细胞，将胚状体培养36天。肝细胞分化标志物在ES细胞分化的细胞中表达。细胞色素P450（CYP450）基因在细胞中的表达模式可分为早中期高表达、晚期表达、全期表达和全期不表达4类。芳烃受体、芳烃受体核转位蛋白和糖皮质激素受体在细胞培养过程中均有表达。孕烷X受体仅在培养24天以上的细胞中检测到。甲胎蛋白和白蛋白分别与CYP3A2和CYP1A1共表达。猴ES细胞也在体外分化为肝细胞。细胞表达甲胎蛋白、白蛋白、CYP3A8、CYP3A66和CYP7A1。我们从分化中的猴ES细胞中分离了一个cDNA克隆，并鉴定了一种新的CYP3A7m亚型。推导的氨基酸序列与CYP3A4、CYP3A5、CYP3A7和CYP3A43的同源性分别为89%、81%、91%和72%。这些结果表明，在从ES细胞分化的肝细胞中表达了转录因子和转录因子基因，并且在分化过程中，这些表达水平和模式在单个酶中发生了显著变化。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of Human Fetal Hepatocytes : Expression and Induction of CYP3As

人胎儿肝细胞的表征：CYP3As 的表达和诱导

DOI：
发表时间：
2005
期刊：
Proceedings of the 15^<th> Intl. Symposium on MDO
影响因子：
0
作者：
A.Hanaki;J.Ueda;N.Ikota;Matsunaga T et al.
通讯作者：
Matsunaga T et al.

Expressions of cytochrome P450 in differentiating mouse embryonic stem cells.

细胞色素P450在分化小鼠胚胎干细胞中的表达。

DOI：
发表时间：
2005
期刊：
Drug Metab Rev 37
影响因子：
0
作者：
Matsunaga T;Kose E;Yasuda S;Ise H;Ikeda U;Ohmori S;松永民秀;Matsunaga T et al.;Maruyama M et al.;Ohmori S et al.;Matsunaga T et al.
通讯作者：
Matsunaga T et al.

Effective NADH-dependent oxidation of 7β-hydroxy-Δ8-tetrahydrocannabinol to the corresponding ketone by Japanese monkey hepatic microsomes

DOI：
10.1248/bpb.28.646
发表时间：
2005-04-01
期刊：
BIOLOGICAL & PHARMACEUTICAL BULLETIN
影响因子：
2
作者：
Matsunaga, T;Higuchi, S;Yamamoto, I
通讯作者：
Yamamoto, I

Simple and highly sensitive method for determination of P-glycoprotein ATPase activity using Luciferase.

使用荧光素酶测定 P-糖蛋白 ATP 酶活性的简单且高度灵敏的方法。

DOI：
发表时间：
2005
期刊：
Drug Metab Rev 37
影响因子：
0
作者：
Matsunaga T;Kose E;Yasuda S;Ise H;Ikeda U;Ohmori S;松永民秀;Matsunaga T et al.;Maruyama M et al.;Ohmori S et al.
通讯作者：
Ohmori S et al.

Induction mechanisms of CYP3As in human fetal hepatocytes by glucocorticoids.

糖皮质激素在人胎儿肝细胞中诱导 CYP3As 的机制。

DOI：
发表时间：
2005
期刊：
Drug Metab Rev 37
影响因子：
0
作者：
Matsunaga T;Kose E;Yasuda S;Ise H;Ikeda U;Ohmori S;松永民秀;Matsunaga T et al.;Maruyama M et al.
通讯作者：
Maruyama M et al.