Long noncoding RNA Q associates with Sox2 and is involved in the maintenance of pluripotency in mouse embryonic stem cells
Long noncoding RNA Q associates with Sox2 and is involved in the maintenance of pluripotency in mouse embryonic stem cells
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长链非编码 RNA Q 与 Sox2 相关，参与小鼠胚胎干细胞多能性的维持
DOI：
10.1002/stem.3180
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发表时间：
2020-05-01
期刊：
影响因子：
5.2
通讯作者：
Zhu, Songcheng
中科院分区：
文献类型：
--
作者：
Jing, Ruiqi;Guo, Xudong;Zhu, Songcheng
大基因间非编码RNA（lincRNA）在胚胎干细胞中可能发挥重要作用，在维持多能性。干细胞特异性lincRNA及其相互作用伴侣的鉴定将加深我们对维持干细胞多能性的理解。我们鉴定了一种lincRNA，LincQ，它在ESC中特异性表达，并受核心多能转录因子的调控。在分化过程中迅速下调。LincQ基因在胚胎干细胞中的敲低导致分化、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基因的外显子1可以与Sox 2特异性结合。Sox2中的Soxp区域，而不是高迁移率族结构域，负责LincQ结合。重要的是，LincQ和Sox 2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Sox 2的关键下游靶标，因为Esrrb和Tfcp2l1的过表达可以恢复由LincQ耗尽诱导的ESC多能性丧失。总之，我们发现LincQ特异性地与Sox 2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。
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.