Embryonic stem cells (ESCs) preserve the unique ability to differentiate into any somatic cell lineage while maintaining their self-renewal potential, relying on a complex interplay of extracellular signals regulating the expression/activity of pluripotency transcription factors and their targets. Leukemia inhibitory factor (LIF)-activated STAT3 drives ESCs’ stemness by a number of mechanisms, including the transcriptional induction of pluripotency factors such as Klf4 and the maintenance of a stem-like epigenetic landscape. However, it is unknown if STAT3 directly controls stem-cell specific non-coding RNAs, crucial to balance pluripotency and differentiation. Applying a bioinformatic pipeline, here we identify Lncenc1 in mouse ESCs as an STAT3-dependent long non-coding RNA that supports pluripotency. Lncenc1 acts in the cytoplasm as a positive feedback regulator of the LIF–STAT3 axis by competing for the binding of microRNA-128 to the 3’UTR of the Klf4 core pluripotency factor mRNA, enhancing its expression. Our results unveil a novel non-coding RNA-based mechanism for LIF–STAT3-mediated pluripotency.

中文翻译：

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STAT3依赖性长非编码RNA Lncenc1通过稳定K mRNA促进小鼠ES细胞的多能性

胚胎干细胞（ESC）保留了分化成任何体细胞谱系的独特能力，同时保持其自我更新潜力，依赖于调节多能性转录因子及其靶标的表达/活性的细胞外信号的复杂相互作用。白血病抑制因子 (LIF) 激活的 STAT3 通过多种机制驱动 ESC 的干性，包括 Klf4 等多能性因子的转录诱导和干样表观遗传景观的维持。然而，尚不清楚 STAT3 是否直接控制干细胞特异性非编码 RNA，这对于平衡多能性和分化至关重要。应用生物信息学流程，我们将小鼠 ESC 中的 Lncenc1 识别为支持多能性的 STAT3 依赖性长非编码 RNA。Lncenc1 在细胞质中作为 LIF-STAT3 轴的正反馈调节因子，通过竞争 microRNA-128 与 Klf4 核心多能因子 mRNA 3'UTR 的结合，增强其表达。我们的结果揭示了一种基于非编码 RNA 的新型 LIF-STAT3 介导的多能性机制。