LincU Preserves Naïve Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.
LincU Preserves Naïve Pluripotency by Restricting ERK Activity in Embryonic Stem Cells.
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LincU 通过限制胚胎干细胞中的 ERK 活性来保留初始多能性
DOI：
10.1016/j.stemcr.2018.06.010
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发表时间：
2018-08-14
影响因子：
5.9
通讯作者：
Kang J
中科院分区：
文献类型：
--
作者：
Jiapaer Z;Li G;Ye D;Bai M;Li J;Guo X;Du Y;Su D;Jia W;Chen W;Wang G;Yu Y;Zhu F;Wan X;Kang J
虽然长链非编码RNA（lncRNA）的功能作用已被越来越多地确定，但很少有lncRNA控制胚胎干细胞（ESC）的幼稚状态。在这里，我们报告了一个幼稚状态相关的lncRNA，LinCU，它在mESC中被Nanog内在激活。LinCU缺陷型mESC表现出致敏样多能状态，并增强从幼稚状态到致敏状态的转变，而异位LinCU表达使mESC维持在幼稚状态。从机制上讲，我们证明LinCU结合并稳定DUSP 9蛋白（一种ERK特异性磷酸酶），然后组成性抑制ERK 1/2信号通路，这对维持幼稚状态至关重要。重要的是，我们揭示了LinCU的功能作用在人类中是进化保守的。因此，我们的研究结果揭示了LinCU是一种保守的lncRNA，它本质上限制了MAPK/ERK活性并维持了ESCs的幼稚状态。LinCU是完整的，足以维持mESC的幼稚状态LinCU结合并稳定DUSP 9蛋白以抑制ERK 1/2磷酸化LinCU是幼稚状态mESC中NANOG的直接靶标LinCU的功能作用在人类ESC中是保守的Kang和同事报告了一种幼稚状态相关的长非编码RNA（LinCU），其直接受Nanog调节，并通过保护ERK特异性磷酸酶DUSP 9免受泛素-蛋白酶体介导的降解来稳定ERK特异性磷酸酶DUSP 9，以维持mESC的幼稚状态。此外，LinCU在人类ESC中功能保守。
Although the functional roles of long noncoding RNAs (lncRNAs) have been increasingly identified, few lncRNAs that control the naïve state of embryonic stem cells (ESCs) are known. Here, we report a naïve-state-associated lncRNA, LincU, which is intrinsically activated by Nanog in mESCs. LincU-deficient mESCs exhibit a primed-like pluripotent state and potentiate the transition from the naïve state to the primed state, whereas ectopic LincU expression maintains mESCs in the naïve state. Mechanistically, we demonstrate that LincU binds and stabilizes the DUSP9 protein, an ERK-specific phosphatase, and then constitutively inhibits the ERK1/2 signaling pathway, which critically contributes to maintenance of the naïve state. Importantly, we reveal the functional role of LincU to be evolutionarily conserved in human. Therefore, our findings unveil LincU as a conserved lncRNA that intrinsically restricts MAPK/ERK activity and maintains the naïve state of ESCs. LincU is integral and sufficient to maintain the naïve state of mESCs LincU binds and stabilizes DUSP9 protein to inhibit the ERK1/2 phosphorylation LincU is a direct target of NANOG in naïve-state mESCs The functional role of LincU is conserved in human ESCs Kang and colleagues report a naïve-state-associated long noncoding RNA (LincU), which is directly regulated by Nanog and stabilizes the ERK-specific phosphatase DUSP9 by protecting it from ubiquitin-proteasome mediated degradation to maintain the naïve state of mESCs. Moreover, LincU is functionally conserved in human ESCs.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
SIRT1/OCT6 轴失调导致环境压力诱发的神经感应缺陷
影响因子：
5.9
作者：
Li G;Jiapaer Z;Weng R;Hui Y;Jia W;Xi J;Wang G;Zhu S;Zhang X;Feng D;Liu L;Zhang X;Kang J
通讯作者：
Kang J
DOI：
10.1098/rstb.2013.0540
发表时间：
2014-12-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kalkan T;Smith A
通讯作者：
Smith A
影响因子：
64.8
作者：
Chambers, Ian;Silva, Jose;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
4.6
作者：
Leitch, Harry G.;Smith, Austin
通讯作者：
Smith, Austin