Long Noncoding RNA Q Associates with Sox2 and Is Involved in the Maintenance of Pluripotency in Mouse Embryonic Stem Cells,STEM CELLS

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Long Noncoding RNA Q Associates with Sox2 and Is Involved in the Maintenance of Pluripotency in Mouse Embryonic Stem Cells
STEM CELLS ( IF 4.0 ) Pub Date : 2020-05-01 , DOI: 10.1002/stem.3180
Ruiqi Jing _{1,

2,

3} , Xudong Guo _{1,

4} , Yiwei Yang ₁ , Wen Chen ₁ , Jiuhong Kang _{1,

5} , Songcheng Zhu ₁

Affiliation

Large intergenic noncoding RNAs (lincRNAs) in ESCs may play an important role in the maintenance of pluripotency. The identification of stem cell‐specific lincRNAs and their interacting partners will deepen our understanding of the maintenance of stem cell pluripotency. We identified a lincRNA, LincQ, which is specifically expressed in ESCs and is regulated by core pluripotent transcription factors. It was rapidly downregulated during the differentiation process. Knockdown of LincQ in ESCs led to differentiation, downregulation of pluripotency‐related genes, and upregulation of differentiation‐related genes. We found that exon 1 of LincQ can specifically bind to Sox2. The Soxp region in Sox2, rather than the high mobility group domain, is responsible for LincQ binding. Importantly, the interaction between LincQ and Sox2 is required for the maintenance of pluripotency in ESCs and the transcription of pluripotency genes. Esrrb and Tfcp2l1 are key downstream targets of LincQ and Sox2, since overexpression of Esrrb and Tfcp2l1 can restore the loss of ESC pluripotency that is induced by LincQ depletion. In summary, we found that LincQ specifically interacts with Sox2 and contributes to the maintenance of pluripotency, highlighting the critical role of lincRNA in the pluripotency regulatory network.

中文翻译：

长链非编码 RNA Q 与 Sox2 相关并参与维持小鼠胚胎干细胞的多能性

ESC 中的大基因间非编码 RNA (lincRNA) 可能在维持多能性中起重要作用。干细胞特异性 lincRNA 及其相互作用伙伴的鉴定将加深我们对维持干细胞多能性的理解。我们确定了一种 lincRNA，LincQ，它在 ESC 中特异性表达并受核心多能转录因子的调节。它在分化过程中迅速下调。在 ESC 中敲低 LincQ 会导致分化、多能性相关基因的下调和分化相关基因的上调。我们发现 LincQ 的外显子 1 可以特异性结合 Sox2。Sox2 中的 Soxp 区域，而不是高迁移率组域，负责 LincQ 绑定。重要的，LincQ 和 Sox2 之间的相互作用是维持 ESC 多能性和多能性基因转录所必需的。Esrrb 和 Tfcp2l1 是 LincQ 和 Sox2 的关键下游目标，因为 Esrrb 和 Tfcp2l1 的过表达可以恢复由 LincQ 消耗引起的 ESC 多能性丧失。总之，我们发现 LincQ 与 Sox2 特异性相互作用并有助于维持多能性，突出了 lincRNA 在多能性调控网络中的关键作用。

更新日期：2020-05-01

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