Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation
文献类型：期刊论文
| 作者 | Jiang, J; Lv, WJ; Ye, XY; Wang, LB; Zhang, M; Yang, H; Okuka, M; Zhou, CK; Zhang, X; Liu, L |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2013 |
| 卷号 | 23期号:1页码:92-106 |
| 关键词 | somatic reprogramming genomic stability telomere Zscan4 tetraploid complementation iPS cells |
| 通讯作者 | Li, JS (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Grp Epigenet Reprogramming, State Key Lab Cell Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,liutelom@yahoo.com ; jsli@sibcb.ac.cn |
| 英文摘要 | Induced pluripotent stem (iPS) cells generated using Yamanaka factors have great potential for use in autologous cell therapy. However, genomic abnormalities exist in human iPS cells, and most mouse iPS cells are not fully pluripotent, as evaluated by the tetraploid complementation assay (TCA); this is most likely associated with the DNA damage response (DDR) occurred in early reprogramming induced by Yamanaka factors. In contrast, nuclear transfer can faithfully reprogram somatic cells into embryonic stem (ES) cells that satisfy the TCA. We thus hypothesized that factors involved in oocyte-induced reprogramming may stabilize the somatic genome during reprogramming, and improve the quality of the resultant iPS cells. To test this hypothesis, we screened for factors that could decrease DDR signals during iPS cell induction. We determined that Zscan4, in combination with the Yamanaka factors, not only remarkably reduced the DDR but also markedly promoted the efficiency of iPS cell generation. The inclusion of Zscan4 stabilized the genomic DNA, resulting in p53 downregulation. Furthermore, Zscan4 also enhanced telomere lengthening as early as 3 days post-infection through a telomere recombination-based mechanism. As a result, iPS cells generated with addition of Zscan4 exhibited longer telomeres than classical iPS cells. Strikingly, more than 50% of iPS cell lines (11/19) produced via this "Zscan4 protocol" gave rise to live-borne all-iPS cell mice as determined by TCA, compared to 1/12 for lines produced using the classical Yamanaka factors. Our findings provide the first demonstration that maintaining genomic stability during reprogramming promotes the generation of high quality iPS cells. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | PLURIPOTENT STEM-CELLS ; SISTER-CHROMATID EXCHANGE ; DNA-DAMAGE ; ES CELLS ; EPIGENETIC MEMORY ; COPY NUMBER ; TELOMERES ; GENERATION ; GENES ; MICE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000313194700013 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/323]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Jiang, J,Lv, WJ,Ye, XY,et al. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation[J]. CELL RESEARCH,2013,23(1):92-106. |
| APA | Jiang, J.,Lv, WJ.,Ye, XY.,Wang, LB.,Zhang, M.,...&Li, JS.(2013).Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation.CELL RESEARCH,23(1),92-106. |
| MLA | Jiang, J,et al."Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation".CELL RESEARCH 23.1(2013):92-106. |
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