體細(xì)胞重編程技術(shù)具有重要的理論和實(shí)踐意義,。在再生醫(yī)學(xué)研究中,，通過(guò)該技術(shù)獲得來(lái)自患者的多能干細(xì)胞，進(jìn)一步用于自體移植可以避免免疫排斥問題,，從而使其成為干細(xì)胞和再生醫(yī)學(xué)研究的熱點(diǎn)領(lǐng)域,。
核移植和iPS技術(shù)均能將體細(xì)胞重編為多能干細(xì)胞，然而兩者的重編程的能力卻不同,。核移植后獲得的胚胎干細(xì)胞（ESCs）具有與正常ESCs相似的多能性,，通過(guò)四倍體囊胚注射能夠獲得小鼠，然而大部分的iPS細(xì)胞卻沒有這一能力,。最近的研究發(fā)現(xiàn),，人的iPS細(xì)胞存在不少的遺傳變異。由此,，可以推測(cè)參與核移植誘導(dǎo)體細(xì)胞重編程的因子可能對(duì)遺傳物質(zhì)的穩(wěn)定起著重要的作用,，如果將這些因子應(yīng)用到iPS技術(shù)中，可能會(huì)維持重編程過(guò)程中細(xì)胞遺傳物質(zhì)的穩(wěn)定性,，從而改善iPS細(xì)胞的質(zhì)量,。
11月13日，國(guó)際學(xué)術(shù)期刊Cell Research在線發(fā)表了中科院上海生科院生化與細(xì)胞所李勁松研究組與南開大學(xué)劉林研究組的最新研究成果,，他們發(fā)現(xiàn)將核移植過(guò)程中的重要因子Zscan4與Yamanaka因子共同使用,，不僅能夠顯著提高iPS細(xì)胞的產(chǎn)生效率，而且降低IPS細(xì)胞形成過(guò)程中DNA的損傷,，顯著地改善了iPS細(xì)胞的質(zhì)量,。
為了獲得對(duì)重編程細(xì)胞的遺傳物質(zhì)能起保護(hù)作用的重要因子，李勁松研究組的蔣婧和呂紋簡(jiǎn)等同學(xué)建立了一個(gè)篩選系統(tǒng),，他們發(fā)現(xiàn)其中Zscan4能顯著提高iPS細(xì)胞的形成效率,。進(jìn)一步研究發(fā)現(xiàn)Zscan4能夠促進(jìn)重編程過(guò)程中細(xì)胞端粒區(qū)以及非端粒區(qū)遺傳物質(zhì)的穩(wěn)定。深入研究發(fā)現(xiàn),，Zscan4能夠快速延長(zhǎng)重編程細(xì)胞的端粒,，重編程后第三天，Zscan4組的細(xì)胞端粒比沒有Zscan4組的長(zhǎng)約5KB,；這種快速的端粒延長(zhǎng)是通過(guò)姐妹染色體互換完成,，而不是通過(guò)傳統(tǒng)的端粒酶介導(dǎo)。由于Zscan4的介入穩(wěn)定了重編程細(xì)胞的基因組,，研究人員發(fā)現(xiàn)iPS細(xì)胞的質(zhì)量得到了顯著地改善,，19株中有11株(58%)通過(guò)四倍體囊胚注射能夠獲得完成來(lái)自iPS細(xì)胞的小鼠，而通過(guò)傳統(tǒng)Yamanaka方法獲得的iPS細(xì)胞,，11株中只有1株能夠獲得完全iPS細(xì)胞的小鼠,。這些結(jié)果提示，在細(xì)胞重編程過(guò)程,，除了多能性的建立,，細(xì)胞遺傳物質(zhì)穩(wěn)定性的維持也非常重要,。這一結(jié)果對(duì)通過(guò)Yamanaka方法獲得iPS細(xì)胞研究注入了新的思路，為獲得更安全iPS細(xì)胞應(yīng)用于再生醫(yī)學(xué)提供了重要的理論依據(jù),。
該項(xiàng)工作得到了國(guó)家科技部,、國(guó)家基金委、中國(guó)科學(xué)院戰(zhàn)略性先導(dǎo)科技專項(xiàng)以及上海市科委經(jīng)費(fèi)的支持,。（生物谷Bioon.com）
doi: 10.1038/cr.2012.157
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Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation.
Jiang J, Lv W, Ye X, Wang L, Zhang M, Yang H, Okuka M, Zhou C, Zhang X, Liu L, Li J.
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
