山中伸弥8月Nature、Cell连发2篇文章 解决癌变和效率问题

　　

生物通报道，山中伸弥在iPS领域的研究热情可谓十分之高，仅从近期他发表的文章数量就能看出，7月份，接连在Nature、Nature Biotechnology上发表两篇文章，不久前的8又在Nature上发表通过抑制p53-p21路径诱导iPS的研究性文章，8月底，又在Cell Stem Cell上发表提高iPS效率的最新文章Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells。

 

在iPS细胞研究过程中，山中伸弥等人发现干细胞总是集中于氧气相对少的地方。于是，他们在利用人体皮肤细胞培养iPS细胞时把培养环境的氧浓度从通常的21%降到5%，发现iPS细胞的生成效率可提高到原来的2.5倍至4.2倍。但如果进一步降低氧浓度到1%，就会适得其反导致部分细胞死亡。

 

研究人员又利用实验鼠的皮肤细胞培养iPS细胞，发现5%的氧浓度也是最合适的。

 

另外一篇Nature文章Suppression of induced pluripotent stem cell generation by the p53–p21 pathway则介绍了诱导iPS时取消c-Myc基因后用siRNA阻断p53有助提高iPS转化效率，有趣的是，不用病毒载体诱导iPS，而用质粒诱导iPS时，阻断p53同样可提高iPS转化率。

 

用芯片分析发现，人和小鼠有34个涉及p53调节的基因，这些基因通过p21-p53通路调控iPS的致癌性和转化效率。

（生物通 小茜）

生物通推荐原文检索

Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells

 

Yoshinori Yoshida1,,,Kazutoshi Takahashi1,Keisuke Okita1,Tomoko Ichisaka2andShinya Yamanaka1,2,3,4,,

 

1 Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan

2 Yamanaka iPS Cell Special Project, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan

3 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

4 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA

 

Main Text

Mouse and human somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by the transduction of four transcription factors, Oct 3/4, Sox2, Klf4, and c-Myc (Maherali etal., 2007,Meissner etal., 2007,Okita etal., 2007,Takahashi etal., 2007,Takahashi and Yamanaka, 2006,Wernig etal., 2007). Patient or disease-specific human iPSCs could be used for studying pathogenesis, or potentially also to treat patients suffering from incurable diseases by transplanting the regenerated grafts derived from their own cells. However, the low induction efficiency and high tumorigenesis rate due to the use of proto-oncogenes, such as c-Myc, continue to hinder the clinical application of iPS technology. Many efforts have been made to find otherfactors or small molecules that facilitate the reprogramming process (Huangfu etal., 2008,Shi etal., 2008b). In this study, we show that conducting reprogramming in hypoxic conditions results in improved efficiency for both mouse and human cells……