Telomeric noncoding RNA promotes mouse embryonic stem cell self-renewal through inhibition of TCF3 activity

被引:9
作者
Xu, Xiaojuan [1 ,2 ]
Guo, Mengmeng [3 ]
Zhang, Na [1 ]
Ye, Shoudong [3 ]
机构
[1] Chinese Acad Sci, Hefei Inst Phys Sci, High Magnet Field Lab, Hefei, Anhui, Peoples R China
[2] Univ Sci & Technol China, Hefei, Anhui, Peoples R China
[3] Anhui Univ, Sch Life Sci, Ctr Stem Cell & Translat Med, 111 Jiu Long Rd, Hefei 230601, Anhui, Peoples R China
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2018年 / 314卷 / 06期
关键词
CHIR; mouse embryonic stem cells; self-renewal; TCF3; TERRA; REPEAT-CONTAINING RNA; PLURIPOTENCY NETWORK; REGULATORY CIRCUITRY; DIFFERENTIATION; TERRA; MICRORNAS; MAINTAINS; TRANSCRIPTION; EXPRESSION; REPRESSION;
D O I
10.1152/ajpcell.00292.2017
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Although long noncoding RNAs (lncRNAs) are emerging as new modulators in the fate deeision of pi impotent stem cells, the functions of specific lncRNAs remain unclear. Here, we found that telomeric RNA (TERRA or TelRNA), one type of lncRNAs, is highly expressed in mouse embryonic stem cells (mESCs) but declines significantly upon differentiation. TERRA is induced by the Wnt/beta-catenin signaling pathway and can reproduce its self-renewal-promoting effect when overexpressed. Further studies revealed that T cell factor 3 (TCF3) is a potential downstream target of TERRA and mediates the effect of TERRA in mESC maintenance. TERRA inhibits TCF3 transcription, while enforced TCF3 expression abrogates the undifferentiated state of mESCs supported by TERRA. Accordingly, the transcripts of the pluripotency genes Esrrb, Tfcp2l1, and Klf2, repressed by TCF3 in mESCs, are increased in TERRA -overexpressing cells. Our study therefore highlights the important role of TERRA in mESC maintenance and also uncovers a mechanism by which TERRA promotes self-renewal. These data will expand our understanding of the pluripotent regulatory network of ESCs.
引用
收藏
页码:C712 / C720
页数:9
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