SummaryThe 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.

Many young adults are in a state of stress due to social and psychological pressures, which may result in male reproductive dysfunction. To provide new insight into this phenomenon, we investigated the effect of stress on the regulation of key genes and biological events in specific stages of spermatogenesis. After establishing rat stress models of different time durations, we observed pathological changes in testis through haematoxylin and eosin staining, and analysed gene expression in testis by RNA-seq, bioinformatic analysis, and reverse transcription qPCR (RT-qPCR). Immunohistochemistry (IHC) with the TissueFAXS quantitative imaging system was used to verify changes of different population of spermatogenic cells marked by differentially expressed marker genes. Our results showed that prolonged stress can lead to pathological changes in the testes, such as thinning of the spermatogenic epithelium, a decreased number of spermatogenic epithelial cells, the disordered arrangement of spermatogenic cells, and a decreased number of mature sperms. RNA-seq revealed that key marker spermatogenesis-related genes such as Stra8, Sycp3, Piwil1, and Tnp1 had significantly decreased expression levels in chronic stress groups, and this was confirmed by RT-qPCR and IHC. Collectively, these findings suggest that chronic stress causes damaging pathological changes in testis and dysregulates the marker genes of specific stages of spermatogenesis and change the population of spermatogenic cells, which may be a critical responsible for male reproductive dysfunction.

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