| Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. | |
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MedLine Citation:
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PMID: 23147797 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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.Cell Research advance online publication 13 November 2012; doi:10.1038/cr.2012.157. |
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Authors:
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Jing Jiang; Wenjian Lv; Xiaoying Ye; Lingbo Wang; Man Zhang; Hui Yang; Maja Okuka; Chikai Zhou; Xuan Zhang; Lin Liu; Jinsong Li |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-13 |
Journal Detail:
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Title: Cell research Volume: - ISSN: 1748-7838 ISO Abbreviation: Cell Res. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9425763 Medline TA: Cell Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Group of Epigenetic Reprogramming, State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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