Li Xiaoyong, Ao Junping, Wu Ji
Renji Hospital, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.
Oncotarget. 2017 Apr 18;8(16):26573-26590. doi: 10.18632/oncotarget.15719.
Accumulating evidence indicates that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) involve in germ cell development. However, little is known about the functions and mechanisms of lncRNAs and circRNAs in self-renewal and differentiation of germline stem cells. Therefore, we explored the expression profiles of mRNAs, lncRNAs, and circRNAs in male and female mouse germline stem cells by high-throughput sequencing. We identified 18573 novel lncRNAs and 18822 circRNAs in the germline stem cells and further confirmed the existence of these lncRNAs and circRNAs by RT-PCR. The results showed that male and female germline stem cells had similar GDNF signaling mechanism. Subsequently, 8115 mRNAs, 3996 lncRNAs, and 921 circRNAs exhibited sex-biased expression that may be associated with germline stem cell acquisition of the sex-specific properties required for differentiation into gametes. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed different functions for these sex-biased lncRNAs and circRNAs. We further constructed correlated expression networks including coding-noncoding co-expression and competing endogenous RNAs with bioinformatics. Co-expression analysis showed hundreds of lncRNAs were correlated with sex differences in mouse germline stem cells, including lncRNA Gm11851, lncRNA Gm12840, lncRNA 4930405O22Rik, and lncRNA Atp10d. CeRNA network inferred that lncRNA Meg3 and cirRNA Igf1r could bind competitively with miRNA-15a-5p increasing target gene Inha, Acsl3, Kif21b, and Igfbp2 expressions. These findings provide novel perspectives on lncRNAs and circRNAs and lay a foundation for future research into the regulating mechanisms of lncRNAs and circRNAs in germline stem cells.
越来越多的证据表明，长链非编码RNA（lncRNA）和环状RNA（circRNA）参与生殖细胞发育。然而，关于lncRNA和circRNA在生殖系干细胞自我更新和分化中的功能及机制知之甚少。因此，我们通过高通量测序探究了雄性和雌性小鼠生殖系干细胞中mRNA、lncRNA和circRNA的表达谱。我们在生殖系干细胞中鉴定出18573个新的lncRNA和18822个circRNA，并通过RT-PCR进一步证实了这些lncRNA和circRNA的存在。结果表明，雄性和雌性生殖系干细胞具有相似的GDNF信号机制。随后，8115个mRNA、3996个lncRNA和921个circRNA表现出性别偏向性表达，这可能与生殖系干细胞获得分化为配子所需的性别特异性特性有关。基因本体论（GO）和KEGG通路富集分析揭示了这些性别偏向性lncRNA和circRNA的不同功能。我们进一步利用生物信息学构建了包括编码-非编码共表达和竞争性内源RNA的相关表达网络。共表达分析表明，数百个lncRNA与小鼠生殖系干细胞中的性别差异相关，包括lncRNA Gm11851、lncRNA Gm12840、lncRNA 4930405O22Rik和lncRNA Atp10d。ceRNA网络推断lncRNA Meg3和cirRNA Igf1r可以与miRNA-15a-5p竞争性结合，增加靶基因Inha、Acsl3、Kif21b和Igfbp2的表达。这些发现为lncRNA和circRNA提供了新的视角，并为未来研究lncRNA和circRNA在生殖系干细胞中的调控机制奠定了基础。
