Telomere reprogramming and maintenance in porcine iPS cells.
Telomere reprogramming and maintenance in porcine iPS cells.
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猪 iPS 细胞的端粒重编程和维持。
DOI：
10.1371/journal.pone.0074202
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Ji G;Ruan W;Liu K;Wang F;Sakellariou D;Chen J;Yang Y;Okuka M;Han J;Liu Z;Lai L;Gagos S;Xiao L;Deng H;Li N;Liu L
端粒重编程和外源基因的沉默已在小鼠和人诱导多能干细胞（iPS细胞）中得到证实。猪有潜力为人类提供异种移植，并模拟和测试人类疾病。我们研究了在不同条件下产生和培养的猪iPS细胞的端粒长度和维持。不同的猪iPS细胞系中端粒长度不同，一些具有端粒延长和维持，而另一些端粒缩短。通过畸胎瘤形成试验，具有足够端粒长度维持的猪iPS细胞显示出体内分化的能力。具有短的或功能失调的端粒的IPS细胞表现出形成畸胎瘤的能力降低。此外，不充分的端粒酶和不完全的端粒重编程和/或维护链接到猪iPS细胞中外源基因的持续激活。相比之下，具有外源基因表达减少或部分外源基因沉默的猪iPS细胞表现出内源性多能基因和端粒酶基因的活化不足，伴随着随着传代次数的增加端粒缩短。此外，在猪iPS细胞中也发现了端粒双联体、端粒姐妹染色单体交换和T环，推测它们参与了端粒通过重组而延长。这些数据表明，在猪iPS细胞的诱导和传代过程中，端粒重编程涉及端粒依赖性和端粒非依赖性机制，但这些都是不够的，导致端粒损伤和缩短增加，染色体不稳定。活性外源基因可能会弥补内源基因激活不足以及猪iPS细胞端粒重编程和维持不完全的问题。对端粒重编程和维持的进一步了解可能有助于提高猪iPS细胞的质量。
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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影响因子：
11.4
作者：
Herrera, E;Samper, E;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
9.1
作者：
Ji GuangZhen;Liu Kai;Liu Lin
通讯作者：
Liu Lin
影响因子：
4.8
作者：
Esteban, Miguel A.;Xu, Jianyong;Pei, Duanqing
通讯作者：
Pei, Duanqing
影响因子：
4
作者：
Alberio, Ramiro;Croxall, Nicola;Allegrucci, Cinzia
通讯作者：
Allegrucci, Cinzia
DOI：
10.1098/rstb.2003.1370
发表时间：
2004-01-29
影响因子：
6.3
作者：
Chan, SRWL;Blackburn, EH
通讯作者：
Blackburn, EH