The Long Noncoding RNA Lncenc1 Maintains Naive States of Mouse ESCs by Promoting the Glycolysis Pathway

Abstract

Summary: 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. : In this article, Bo Wen and colleagues show that Lncenc1, a long noncoding highly RNA abundant in naive ESCs (nESC), maintains self-renewal of nESCs by controlling glycolytic activity. Lncenc1 interacts with HNRNPK and PTBP1, which function as a complex activator of glycolysis gene expression. These results suggested roles of lncRNAs in linking energy metabolism and naive pluripotency. Keywords: lncRNA, glycolysis, metabolism, pluripotent stem cells, naive pluripotency, Lncenc1, embryonic stem cell