Telomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells
Telomeres Acquire Embryonic Stem Cell Characteristics in Induced Pluripotent Stem Cells
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DOI：
10.1016/j.stem.2008.12.010
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发表时间：
2009-02-06
期刊：
影响因子：
23.9
通讯作者：
Blasco, Maria A.
中科院分区：
文献类型：
--
作者：
Marion, Rosa M.;Strati, Katerina;Blasco, Maria A.
端粒缩短与生物体衰老有关。PS细胞最近已经从老年患者中获得，然而，尚不清楚端粒染色质是否获得与ES细胞相同的特征。我们在这里表明，端粒延长PS细胞相比，父母分化的细胞时，使用四个（Oct 3/4，Sox 2，Klf 4，cMyc）或三个（Oct 3/4，Sox 2，Klf 4）重编程因子，无论是从年轻人和老年人。我们从遗传学上证明，在重编程过程中，端粒延长通常由端粒酶介导，PS端粒获得ES细胞的表观遗传标记，包括低密度的三甲基化组蛋白H3 K9和H4 K20和端粒转录物的丰度增加。最后，来自越来越多代端粒酶缺陷小鼠的细胞的重编程效率显示PS细胞效率的急剧下降，这是通过端粒酶重新引入恢复的缺陷。总之，这些结果突出了端粒生物学对PS细胞生成和功能的重要性。
Telomere shortening is associated with organismal aging. PS cells have been recently derived from old patients; however, it is not known whether telomere chromatin acquires the same characteristics as in ES cells. We show here that telomeres are elongated in PS cells compared to the parental differentiated cells both when using four (Oct3/4, Sox2, Klf4, cMyc) or three (Oct3/4, Sox2, Klf4) reprogramming factors and both from young and aged individuals. We demonstrate genetically that, during reprogramming, telomere elongation is usually mediated by telomerase and that PS telomeres acquire the epigenetic marks of ES cells, including a low density of tri-methylated histones H3K9 and H4K20 and increased abundance of telomere transcripts. Finally, reprogramming efficiency of cells derived from increasing generations of telomerase-deficient mice shows a dramatic decrease in PS cell efficiency, a defect that is restored by telomerase reintroduction. Together, these results highlight the importance of telomere biology for PS cell generation and functionality.