Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells.
Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells.
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Tcstv1 和 Tcstv3 延长小鼠 ES 细胞的端粒。
DOI：
10.1038/srep19852
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发表时间：
2016-01-27
影响因子：
4.6
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zhang Q;Dan J;Wang H;Guo R;Mao J;Fu H;Wei X;Liu L
小鼠胚胎干细胞(ESC)培养显示出一种异质性的亚稳细胞混合物，零星地进入2-细胞(2C)-类胚胎状态，这对ESC的效力至关重要。2-细胞基因之一，Zscan4，已被证明与小鼠胚胎干细胞的端粒维持、基因组稳定性和多能性有关。胚胎干细胞中其他2C基因的功能仍然难以捉摸。在这里，我们证明了2C基因Tcstv1和Tcstv3在调节端粒长度方面发挥了作用。过表达或敲除Tcstv1和Tcstv3不会立即影响ESCs的体外增殖、多能性和分化。然而，异位表达Tcstv1或Tcstv3会导致端粒延长，而Tcstv1/3基因敲除会缩短ESCs的端粒。Tcstv1或Tcstv3的过表达不会改变端粒的稳定性。此外，Tcstv1还可通过端粒姐妹染色单体交换(T-SCE)增加Zscan4蛋白水平和端粒重组。Tcstv1/3的缺失降低了Zscan4的蛋白水平。Tcstv1和Tcstv3共同参与小鼠胚胎干细胞长期自我更新所需的端粒维持。我们的数据还表明，Tcstv1/3可能协同稳定Zscan4蛋白，但其分子基础仍有待确定。
Mouse embryonic stem cell (ESC) cultures exhibit a heterogeneous mixture of metastable cells sporadically entering the 2-cell (2C)-embryo-like state, critical for ESC potency. One of 2-cell genes, Zscan4, has been shown to be responsible for telomere maintenance, genomic stability and pluripotency of mouse ESCs. Functions of other 2C-genes in ESCs remain elusive. Here we show that 2C-genes Tcstv1 and Tcstv3 play a role in regulation of telomere lengths. Overexpression or knockdown Tcstv1 and Tcstv3 does not immediately affect proliferation, pluripotency and differentiation in vitro of ESCs. However, ectopic expression of Tcstv1 or Tcstv3 results in telomere elongation, whereas Tcstv1/3 knockdown shortens telomeres of ESCs. Overexpression of Tcstv1 or Tcstv3 does not alter telomere stability. Furthermore, Tcstv1 can increase Zscan4 protein levels and telomere recombination by telomere sister chromatid exchange (T-SCE). Depletion of Tcstv1/3 reduces Zscan4 protein levels. Together, Tcstv1 and Tcstv3 are involved in telomere maintenance that is required for long-term self-renewal of mouse ESCs. Our data also suggests that Tcstv1/3 may co-operate and stabilize Zscan4 protein but the molecular bases remain to be determined.