Hes1基因诱导小鼠肝原始细胞分化为胆管上皮细胞

doi:10.3969/j.issn.1004-616x.2008.06.002

癌变·畸变·突变 ›› 2008, Vol. 20 ›› Issue (6): 424-428.doi: 10.3969/j.issn.1004-616x.2008.06.002

Hes1基因诱导小鼠肝原始细胞分化为胆管上皮细胞

田棣，李文林，攸　璞，金彩霞，朱　吉，张　南，胡以平

第二军医大学细胞生物学教研室，上海　200433

收稿日期:2008-09-19 修回日期:2008-10-13 出版日期:2008-11-30 发布日期:2008-11-30

Hes1 Induced Differentiation of Mouse Liver Progenitor Cells to Cholangiocytes

TIAN Di, LI Wen-lin,YOU Pu, JIN Cai-xia, ZHU Ji, ZHANG Nan, HU Yi-ping

Department of Cell Biology of Second Military Medical University, Shanghai 200433, China

Received:2008-09-19 Revised:2008-10-13 Online:2008-11-30 Published:2008-11-30

摘要/Abstract

摘要： 背景与目的：采用体外获得性表达外源发状分裂相关增强子-1(hairy and enhancer of split 1,Hes1)基因的方法，探讨Hes1在肝干细胞分化以及胆管上皮细胞发育中的作用。材料与方法：通过PCR方法从小鼠基因组中克隆Hes1基因片段，构建表达载体pEGFP-C1-Hes1和pcDNA3.1- Hes1，将2种表达载体分别转染肝原始细胞系(LEPCs) ，应用RT-PCR和Real-time PCR技术检测胆管细胞分子标志物CK19、GGT，胆管上皮细胞相关转录因子HNF6、HNF1β，肝细胞分子标志物GS、BGP和肝卵圆细胞的分子标志物Thy-1的表达，并在荧光显微镜下观察EGFP标记的LEPCs细胞系荧光强度的变化。结果：成功构建表达载体pEGFP-C1- Hes1和pcDNA3.1-Hes1。RT-PCR和Real-time PCR检测均表明胆管细胞分子标志CK19、GGT表达量上调；胆管上皮细胞相关转录因子HNF6、HNF1β表达上调；肝细胞分子标志GS、BGP表达量下调；卵圆细胞的分子标志Thy-1表达量下调；LEPCs细胞系绿色荧光增强。结论：初步证明小鼠肝原始细胞经Hes1的表达诱导后可向胆管上皮细胞方向分化，推测Hes1为胆管上皮细胞分化的转录调控因子。

关键词: Hes1, 肝原始细胞, 分化, 胆管上皮细胞

Abstract: BACKGROUND AND AIM: To study the differentiation of mouse liver epithelial progenitor cells(LEPCs) to cholangiocytes induced by hairy and enhancer of split 1(Hes1)gene in vitro. MATERIALS AND METHODS: The Hes1 gene was amplified by PCR from mouse tail genomic DNA and subcloned into pEGFP-C1 and pcDNA3.1 vector．LEPCs were transfected and performed in vitro. Cholangiocyte markers, CK19, GGT, HNF6 and HNF1β; hepatocyte markers, GS and BGP; hepatic oval cell marker, Thy-1 were assayed with RT-PCR and Real-time PCR. The fluorescence of the LEPCs tagged with EGFP was observed in vitro. RESULTS: Cholangiocyte markers, CK19, GGT, HNF6 and HNF1β, were up-regulated. Hepatocyte markers GS and BGP, and hepatic oval cell marker Thy-1, were down- regulated. CONCLUSION: It indicated that LEPCs differentiated to cholangiocytes initially in vitro. and Hes1 might play important roles in the differentiation of LEPCs and influence cholangiocyte versus hepatocyte fate determination.

Key words: Hes1, liver epithelial progenitor cell, differentiation, cholangiocyte

田棣, 李文林, 攸　璞, 金彩霞, 朱　吉, 张　南, 胡以平. Hes1基因诱导小鼠肝原始细胞分化为胆管上皮细胞[J]. 癌变·畸变·突变, 2008, 20(6): 424-428.

TIAN Di, LI Wen-lin, YOU Pu, JIN Cai-xia, ZHU Ji, ZHANG Nan, HU Yi-ping. Hes1 Induced Differentiation of Mouse Liver Progenitor Cells to Cholangiocytes[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2008, 20(6): 424-428.

[1]	虞欣璐, 于兵, 王辰, 张红霞, 朱海英. 基于四环素诱导型Hnf1β和Foxa3表达载体的小鼠胚胎成纤维细胞转分化为肝干细胞的实验体系研究[J]. 癌变·畸变·突变, 2021, 33(3): 163-171.
[2]	伏琼, 唐文娟, 程勇, 贺仁政, 梁冰. 漆姑草醇提物对白血病细胞K562的诱导分化作用[J]. 癌变·畸变·突变, 2021, 33(1): 37-41.
[3]	唐文娟, 伏琼, 程勇, 罗世成, 梁冰. 漆姑草醇提物对人急性早幼粒白血病细胞的诱导分化作用[J]. 癌变·畸变·突变, 2021, 33(1): 42-47.
[4]	王耀坤, 陈珏晓, 张明远, 邵长利, 杨玉, 商宇. 基于数据库的未分化甲状腺癌基因组变异分析及靶向药物筛选[J]. 癌变·畸变·突变, 2021, 33(1): 53-57.
[5]	黄壮程, 王宏浩, 沈沛麟, 林明恩, 何学军. Notch信号通路相关蛋白在腺性膀胱炎和膀胱癌中的表达与意义[J]. 癌变·畸变·突变, 2018, 30(5): 374-377,383.
[6]	袁惟芯，江燕萍，谢春姣，秦飞，陈韵聪，魏青，曾晓雯，沙焱，肖勇梅，*. miR-146a对氢醌抑制HL-60细胞分化的调控作用[J]. 癌变·畸变·突变, 2014, 26(3): 165-170.
[7]	张玉媛，王取南，王允，高金霞，申玲. 镉对小鼠胚胎神经干细胞向胶质细胞分化的影响[J]. , 2012, 24(1): 39-41.
[8]	金彩霞, 李文林, 李元杰, 徐方, 胡以平. 胰岛素启动子在肝干细胞分化研究中的应用[J]. 癌变·畸变·突变, 2010, 22(3): 171-174.
[9]	胡元庆(综述), 卫广森(审校). 有丝分裂原诱导基因-2的研究进展[J]. 癌变·畸变·突变, 2009, 21(4): 327-328.
[10]	李俊新1,单保恩2. 香加皮水提物抑制诱导红白血病细胞K562分化的初步研究[J]. , 2008, 20(6): 449-450.
[11]	段玉清1,2/ 张海晖1/ 吴　佳2/ 谢笔钧2. 莲房原花青素对黑色素瘤B16细胞的诱导分化作用[J]. , 2007, 19(5): 377-380.
[12]	杨立业黄天华. 脂肪组织干细胞的研究进展[J]. , 2007, 19(2): 162-164.
[13]	陶欣荣1,2；李文林1；苏　娟1；王新民1；李建秀1；胡以平1,. 人骨髓间充质干细胞在新生小鼠脑中的植入和分化[J]. , 2007, 19(1): 4-007.
[14]	周　莉；吴纯启；廖明阳. 羟基脲对大鼠胚胎中脑细胞增殖和分化的影响[J]. , 2007, 19(1): 22-025.
[15]	杜　芸；杨会钗；王永军；王小玲；吴国祥；左连富. 食管早期鳞癌的神经内分泌分化及其意义[J]. , 2006, 18(6): 459-461.

Hes1基因诱导小鼠肝原始细胞分化为胆管上皮细胞

Hes1 Induced Differentiation of Mouse Liver Progenitor Cells to Cholangiocytes

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价