Efficient generation of functional hepatocytes from human induced pluripotent stem cells and isolation of hepatic progenitor cells

从人诱导多能干细胞中高效生成功能性肝细胞并分离肝祖细胞

• 批准号: 23790193
• 负责人: SASAKI Takamitsu
• 金额: $ 2.75万
• 依托单位: Tohoku Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790193/
• 关键词: 薬物動態; 代謝学; iPS 細胞; 肝分化誘導法; CYP; 肝特異的転写因子; HNF; iPS細胞; トランスポーター; 転写因子

The purpose of this study was to establish the generation of functional hepatocytes from human induced pluripotent stem cells (iPSCs). It revealed that the hepatic differentiation method using human HNF6-expressing adenovirus contributed to the efficient development of hepatocytes from iPSCs. HNF6 was introduced into the iPSHCs, CYP3A4 expression dramatically increased and the cells had the capability to metabolize testosterone. Our study proved for the first time that HNF6 transactivates the CYP3A4gene in hepatocyte-like cells differentiated from iPSCs.

本研究的目的是确定从人类诱导多能干细胞 (iPSC) 中产生功能性肝细胞。结果表明，使用表达人 HNF6 的腺病毒的肝分化方法有助于 iPSC 肝细胞的有效发育。 HNF6被引入iPSHC中，CYP3A4表达显着增加，并且细胞具有代谢睾酮的能力。我们的研究首次证明HNF6反式激活iPSC分化的肝细胞样细胞中的CYP3A4基因。

项目成果

Hepatocyte nuclear factor-6 enhances expression of CYP3A4 in HepG2 cells and hepatocyte-like cells differentiated from human induced pluripotent stem cells

肝细胞核因子6增强HepG2细胞和人诱导多能干细胞分化的肝细胞样细胞中CYP3A4的表达

• 发表时间: 2011
• 作者: Sasaki T; Tanaka Y; Takahashi S; Kumagai T; Sakaguchi S; Matsunaga T; Nagata K
• 通讯作者: Nagata K

Progression of Alcoholic and Non-alcoholic Steatohepatitis: Common Metabolic Aspects of Innate Immune System and Oxidative Stress

酒精性和非酒精性脂肪性肝炎的进展：先天免疫系统和氧化应激的常见代谢方面

• DOI: 10.2133/dmpk.dmpk-10-rv-087
• 发表时间: 2011
• 影响因子: 2.1
• 作者: Sakaguchi S; Takahashi S; Sasaki T; Kumagai T; Nagata K
• 通讯作者: Nagata K

Enhanced expression of cytochrome P450 genes by hepatocyte nuclear factor-6 in hepatocyte-likecells differentiated from human induced pluripotent stem cells

肝细胞核因子6增强人诱导多能干细胞分化的肝细胞样细胞中细胞色素P450基因的表达

• 发表时间: 2012
• 作者: Takahashi S

Hepatocyte Nuclear Factor 6 Activates the Transcription of CYP3A4 in Hepatocyte-like Cells Differentiated from Human Induced Pluripotent Stem Cells

肝细胞核因子6激活人诱导多能干细胞分化的肝细胞样细胞中<i>CYP3A4</i>的转录

• DOI: 10.2133/dmpk.dmpk-12-rg-132
• 发表时间: 2013
• 影响因子: 2.1
• 作者: Sasaki T; Takahashi S; Numata Y; Narita M; Tanaka Y; Kondo Y; Matsunaga T; Ohmori S; Nagata K
• 通讯作者: Nagata K

Enhanced expression of cytochrome P450 genes by hepatocyte nuclear factor-6 in hepatocyte-like cells differentiated from human induced pluripotent stem cells

肝细胞核因子6增强人诱导多能干细胞分化的肝细胞样细胞中细胞色素P450基因的表达

• 发表时间: 2012
• 作者: Shogo Takahashi