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.

本研究的目的是建立人类诱导多能干细胞（iPSCs）产生功能性肝细胞的方法。结果表明，利用表达人hnf6的腺病毒进行肝分化的方法有助于从iPSCs中高效地发育成肝细胞。将HNF6引入iPSHCs后，CYP3A4表达显著增加，细胞具有睾酮代谢能力。我们的研究首次证实了HNF6在iPSCs分化的肝细胞样细胞中可转激活cyp3a4基因。

项目成果

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: 亀尾肇;石井翔;中沢浩;竹澤 浩気・村瀬 隆史・藤田 誠;水野 善文;本間 雄太;神山 祐・村瀬 隆史・藤田 誠;Takahashi S
• 通讯作者: Takahashi S

Association between Cancer Risk and Drug-metabolizing Enzyme Gene (CYP2A6, CYP2A13, CYP4B1, SULT1A1, GSTM1, and GSTT1) Polymorphisms in Cases of Lung Cancer in Japan

• DOI: 10.2133/dmpk.dmpk-11-rg-046
• 发表时间: 2011-01-01
• 期刊: DRUG METABOLISM AND PHARMACOKINETICS
• 影响因子: 2.1
• 作者: Tamaki, Yuichiro;Arai, Tomio;Hiratsuka, Masahiro
• 通讯作者: Hiratsuka, Masahiro

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: S. Sato;T. Murase;M. Fujita;亀尾肇;Shogo Takahashi
• 通讯作者: Shogo Takahashi

肝特異的転写因子 HNF-6 による薬物代謝酵素発現誘導:新規薬物代謝研究ツールを志向した肝分化 iPS 細胞樹立への応用

肝脏特异性转录因子HNF-6诱导药物代谢酶表达：在建立肝脏分化iPS细胞作为新型药物代谢研究工具中的应用

• 发表时间: 2012
• 作者: Hajime Kameo ;Hiroshi Nakazawa;島田 貴士;佐々木 崇光
• 通讯作者: 佐々木 崇光

Indirubin, a compornent of Ban-Lan-Gen, activates CYP3A4 gene transcription through human pregnane X receptor

Ban-Lan-Gen 的成分靛玉红通过人孕烷 X 受体激活 CYP3A4 基因转录

• 发表时间: 2011
• 作者: H. Nakazawa;M. Kamitani;R. Tada;K. Fukumoto;and M. Itazaki;亀尾肇;Kumagai T
• 通讯作者: Kumagai T