端粒
重编程
端粒酶
诱导多能干细胞
生物
细胞生物学
基因沉默
端粒酶逆转录酶
基因组不稳定性
分子生物学
遗传学
基因
胚胎干细胞
DNA损伤
DNA
作者
Guangzhen Ji,Weimin Ruan,Kai Liu,Fang Wang,Despoina Sakellariou,Ji‐Jun Chen,Yang Yang,Maja Okuka,Jianyong Han,Liu Z,Liangxue Lai,Sarantis Gagos,Lei Xiao,Hongkui Deng,Ning Li,Lin Liu
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2013-09-30
卷期号:8 (9): e74202-e74202
被引量:23
标识
DOI:10.1371/journal.pone.0074202
摘要
Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.
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