MOE Key Laboratory of Metabolism and Molecular Medicine, School of Basic Medical Sciences, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
The Fifth People's Hospital of Shanghai, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; MOE Key Laboratory of Metabolism and Molecular Medicine, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200438, China.
Stem Cell Reports. 2018 Sep 11;11(3):741-755. doi: 10.1016/j.stemcr.2018.08.001. Epub 2018 Aug 30.
The naive embryonic stem cells (nESCs) display unique characteristics compared with the primed counterparts, but the underlying molecular mechanisms remain elusive. Here we investigate the functional roles of Lncenc1, a highly abundant long noncoding RNA in nESCs. Knockdown or knockout of Lncenc1 in mouse nESCs leads to a significantly decreased expression of core pluripotency genes and a significant reduction of colony formation capability. Furthermore, upon the depletion of Lncenc1, the expression of glycolysis-associated genes is significantly reduced, and the glycolytic activity is substantially impaired, as indicated by a more than 50% reduction in levels of glucose consumption, lactate production, and extracellular acidification rate. Mechanistically, Lncenc1 interacts with PTBP1 and HNRNPK, which regulate the transcription of glycolytic genes, thereby maintaining the self-renewal of nESCs. Our results demonstrate the functions of Lncenc1 in linking energy metabolism and naive state of ESCs, which may enhance our understanding of the molecular basis underlying naive pluripotency.
未成熟的胚胎干细胞（nESCs）与已分化的细胞相比具有独特的特性，但潜在的分子机制仍不清楚。在这里，我们研究了高度丰富的长非编码 RNA Lncenc1 在 nESCs 中的功能作用。在小鼠 nESCs 中敲低或敲除 Lncenc1 会导致核心多能性基因的表达显著降低，集落形成能力显著降低。此外，在 Lncenc1 耗尽后，糖酵解相关基因的表达显著降低，糖酵解活性受到严重损害，葡萄糖消耗、乳酸生成和细胞外酸化率水平降低超过 50%。在机制上，Lncenc1 与 PTBP1 和 HNRNPK 相互作用，调节糖酵解基因的转录，从而维持 nESCs 的自我更新。我们的结果表明 Lncenc1 在连接能量代谢和 ESCs 的原始状态方面的功能，这可能有助于我们理解原始多能性的分子基础。
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