Zeng Sicong, Liu Lvjun, Sun Yi, Lu Guangxiu, Lin Ge
Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.
National Engineering and Research Center of Human Stem Cell, Changsha, China.
FASEB J. 2017 Nov;31(11):4783-4795. doi: 10.1096/fj.201600939RR. Epub 2017 Aug 1.
This study aimed to explore the role of telomeric repeat-containing RNA (TERRA) in telomeric chromatin remodeling during the early expansion of human embryonic stem cells (hESCs). During the derivation of hESCs, histone demethylation in the telomeric region facilitates telomerase-mediated telomere elongation. An adequate telomere repeat is essential for hESCs to acquire and/or maintain the unlimited symmetric division, which suggests that there is a link between pluripotency and telomere maintenance. The present study found that the gradual decrease in TERRA levels and related TERRA foci were correlated with telomeric length elongation in the early expansion of hESCs. In addition, TERRA participated in telomeric chromatin remodeling by cooperating with SUV39H1 (suppressor of variegation 3-9 homolog 1/2) to propagate telomeric heterochromatin marker, histone H3 trimethylation of lysine 9. Moreover, the fibroblast growth factor signaling pathway, which is activated in hESCs, could suppress TERRA levels telomeric repeat factor 1, which results in reduced SUV39H1 recruitment by TERRA at the telomere. Taken together, these results highlight the role of TERRA in hESC telomere elongation and homeostasis in the acquisition and/or maintenance of stem cell pluripotency.-Zeng, S., Liu, L., Sun, Y., Lu, G., Lin, G. Role of telomeric repeat-containing RNA in telomeric chromatin remodeling during the early expansion of human embryonic stem cells.
本研究旨在探讨含端粒重复序列的RNA（TERRA）在人类胚胎干细胞（hESCs）早期扩增过程中端粒染色质重塑中的作用。在hESCs的分离过程中，端粒区域的组蛋白去甲基化促进了端粒酶介导的端粒延长。足够的端粒重复序列对于hESCs获得和/或维持无限对称分裂至关重要，这表明多能性与端粒维持之间存在联系。本研究发现，在hESCs早期扩增过程中，TERRA水平的逐渐降低和相关TERRA灶与端粒长度延长相关。此外，TERRA通过与SUV39H1（异染色质抑制因子3-9同源物1/2）协同作用来传播端粒异染色质标记物——赖氨酸9的组蛋白H3三甲基化，从而参与端粒染色质重塑。此外，在hESCs中被激活的成纤维细胞生长因子信号通路可以抑制TERRA水平和端粒重复因子1，这导致TERRA在端粒处招募的SUV39H1减少。综上所述，这些结果突出了TERRA在hESCs端粒延长和稳态维持以及干细胞多能性获得和/或维持中的作用。——曾，S.，刘，L.，孙，Y.，卢，G.，林，G.含端粒重复序列的RNA在人类胚胎干细胞早期扩增过程中端粒染色质重塑中的作用
