Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, People's Republic of China.
Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
Stem Cells. 2020 Jul;38(7):834-848. doi: 10.1002/stem.3180. Epub 2020 May 1.
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.
长链非编码 RNA（lncRNA）在胚胎干细胞中可能在维持多能性方面发挥重要作用。鉴定干细胞特异性 lincRNA 及其相互作用的伙伴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，它在胚胎干细胞中特异性表达，并受核心多能转录因子调控。它在分化过程中迅速下调。在胚胎干细胞中敲低 LincQ 导致分化、多能性相关基因下调和分化相关基因上调。我们发现 LincQ 的外显子 1可以特异性地结合 Sox2。Sox2 中的 Soxp 区域，而不是高迁移率族蛋白结构域，负责 LincQ 结合。重要的是，LincQ 和 Sox2 之间的相互作用对于维持胚胎干细胞的多能性和多能性基因的转录是必需的。Esrrb 和 Tfcp2l1 是 LincQ 和 Sox2 的关键下游靶标，因为过表达 Esrrb 和 Tfcp2l1 可以恢复由 LincQ 耗竭诱导的 ESC 多能性丧失。总之，我们发现 LincQ 特异性地与 Sox2 相互作用，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。
