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 Cell Research (IF:4.2)
Derivation and transcriptional profiling analysis of pluripotent stem cell lines from rat blastocysts
Chunliang Li, Ying Yang, Junjie Gu, Yu Ma and Ying Jin
Cell Res advance online publication, November 4, 2008; doi:10.1038/cr.2008.301
胚胎干细胞是从早期囊胚中体外建立的一类具有自我更新和分化全能性的细胞，这种细胞被视为早期胚胎发育研究和细胞移植治疗的理想来源，小鼠和人的胚胎干细胞已经日趋成熟，但是对于另外一种模式动物大鼠来说，却一直没能建立胚胎干细胞系。中科院健康科学研究所博士生李春亮在金颖教授的指导下在大鼠早期囊胚中成功定位到全能性细胞，并研制出优化的大鼠胚胎干细胞培养基，这种培养环境下全能性基因Oct4阳性的细胞可以大量扩增，同时还表达全能性的标志基因AKP， Nanog和Tra-1-60，在体外悬浮和撤生长因子状态下，这些细胞可以分化成为三胚层来源的细胞，将它们注射到免疫缺陷小鼠中可以获取畸胎瘤，苏木精伊红染色以及聚合酶链式反应证明这些瘤组织中存在三胚层来源的组织，并且特异来源于大鼠。另外研究者还对大鼠类胚胎干细胞的基因表达谱进行了分析，发现了大鼠区别于小鼠和人胚胎干细胞的一套特异调控未分化状态的基因表达网络，对大鼠胚胎干细胞的培养优化提供了宝贵的信息。研究结果于2008年11月4日在线发表于Cell Research杂志（IF=4.2）。 |
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Cell Research (IF:4.2)
WWP2 promotes degradation of transcription factor OCT4 in human pluripotent stem cells
Huiming Xu, Weicheng Wang, Chunliang Li, Hongyao Yu, Acong Yang, Beibei Wang, Ying Jin.
Accepted by Cell Research, 2008. Nov.21th
转录因子OCT4在维持人胚胎干细胞自我更新中具有至关重要的作用，但是对于OCT4蛋白水平调控的分子机制却鲜有报道，中科院健康科学研究所助理研究员徐辉明成功克隆了E3连接酶人WWP2蛋白，证明这个蛋白可以在体内和体外和OCT4存在特异性的相互作用，并对OCT4进行泛素化修饰，修饰后的OCT4会进入26S蛋白酶体降解，进一步的研究发现了WWP2蛋白上介导泛素化过程的关键结构域和氨基酸序列，突变这些氨基酸序列后WWP2蛋白介导的泛素化降解消失。当采用RNAi干扰技术降低WWP2蛋白量时，OCT4的蛋白表达可以得到提升，同时分化相关的标志基因会发生上调，结合分化过程中的WWP2的变化，提示我们WWP2在发育过程中非常重要。以上研究第一次明确了人WWP2蛋白在蛋白水平调控OCT4的重要作用，为人胚胎干细胞维持自我更新机制的研究做出了重要的贡献。以上研究结果被Cell Research杂志（IF=4.2）与2008年11月21日接收发表。 |
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