Analysis of telomere length variation and Shelterin complex subunit gene expression changes in ethanol-exposed human embryonic stem cells.
Analysis of telomere length variation and Shelterin complex subunit gene expression changes in ethanol-exposed human embryonic stem cells.
复制标题
DOI：
10.1016/j.jpsychires.2020.11.027
复制
发表时间：
2021-11
影响因子：
4.8
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Moazzam M;Yim T;Kumaresan V;Henderson DC;Farrer LA;Zhang H
端粒保护染色体末端不被降解。端粒长度（TL）可以通过老化和环境胁迫而改变。在酒精依赖受试者的外周血白细胞和暴露于酒精的体细胞中观察到缩短的TL。为了了解乙醇对多能干细胞中端粒的影响，我们研究了乙醇对TL的影响以及人胚胎干细胞（hESC）中6个Shelterin复合物亚基或端粒调节基因（POT1，RAP 1，TIN 2，TPP 1，TRF 1和TRF 2）的表达，这些细胞暴露于0，25，50或100 mM乙醇中3，7或14天。乙醇诱导的TL和Shelterin复合物亚基基因表达的变化进行了研究，通过定量聚合酶链反应。双因素方差分析表明，TL变异和4个相关Shelterin复合物亚基基因（POT1、TPP1、TIN 2和TRF2）的表达变化主要依赖于乙醇暴露时间的长短，而TRF1和RAP 1的表达受乙醇浓度、暴露时间以及乙醇浓度与暴露时间交互作用的影响。Tukey的多重比较检验表明，TL和POT1，RAP 1，TIN 2，TPP1和TRF 1的表达在7天（与3天相比）乙醇暴露后降低。然而，所有六个Shelterin复合物亚基基因的表达降低恢复和TL没有进一步缩短后，14天（与7天）乙醇暴露，可能是由于适应的hESC乙醇诱导的压力。我们的研究提供了进一步的证据表明，在乙醇胁迫下，TL是由端粒调节基因在干细胞中调节和维持的。
Telomeres protect chromosome ends from degradation. Telomere length (TL) can be altered by aging and environmental stress. Shortened TL has been observed in peripheral blood leukocytes of alcohol dependent subjects and ethanol-exposed somatic cells. To understand the impact of ethanol on telomeres in pluripotent stem cells, we investigated the influence of ethanol on TL and the expression of six Shelterin complex subunit or telomere-regulating genes (POT1, RAP1, TIN2, TPP1, TRF1, and TRF2) in human embryonic stem cells (hESCs), which were exposed to 0, 25, 50, or 100 mM of ethanol for 3, 7, or 14 days. Ethanol-induced TL and Shelterin complex subunit gene expression changes were examined by quantitative polymerase chain reactions. Two-way ANOVA tests indicated that TL variation and expression changes of four associated Shelterin complex subunit genes (POT1, TPP1, TIN2, and TRF2) were mainly dependent on the length of ethanol exposure, while TRF1 and RAP1expression was influenced by ethanol concentration, exposure time, and the interaction of ethanol concentration and exposure time. Tukey’s multiple comparison tests showed that TL and the expression of POT1, RAP1, TIN2, TPP1, and TRF1 were decreased after a 7-day (versus a 3-day) ethanol exposure. However, the decreased expression of all six Shelterin complex subunit genes was recovered and TL was not further shortened after a 14-day (versus a 7-day) ethanol exposure, likely due to the adaptation of hESCs to ethanol-induced stress. Our study provided further evidence that TL is regulated and maintained by telomere-regulating genes in stem cells under ethanol stress.
登录
查看更多内容
影响因子：
4.3
作者：
Anahi Coll, Tamara;Chaufan, Gabriela;Cebral, Elisa
通讯作者：
Cebral, Elisa
影响因子：
14.9
作者：
Necasová I;Janoušková E;Klumpler T;Hofr C
通讯作者：
Hofr C
影响因子：
30.8
作者：
Kim, SH;Kaminker, P;Campisi, J
通讯作者：
Campisi, J
DOI：
10.1038/nrm2848
发表时间：
2010-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4
作者：
Guo, Yanfang;Yu, Haining
通讯作者：
Yu, Haining