s The Expression Profiles of lncRNAs and Their Regulatory Network During Smek1/2 Knockout Mouse Neural Stem Cells Differentiation

Background: Previous studies indicated that the cell fate of neural stem cells (NSCs) after differentiation is determined by Smek1, one isoform of suppressor of Mek null (Smek). Smek deficiency prevents NSCs from differentiation, thus affects the development of nervous system. In recent years, lncRNAs have been found to participate in numerous developmental and biological pathways. However, the effects of knocking out Smek on the expression profiles of lncRNAs during the differentiation remain unknown. Objective: This study is to explore the expression profiles of lncRNAs and their possible function during the differentiation from Smek1/2 knockout NSCs. Methods: We obtained NSCs from the C57BL/6J mouse fetal cerebral cortex. One group of NSCs was from wildtype mouse (WT group), while another group was from knocked out Smek1/2 (KO group). Results: By analyzing the RNA-Seq data, we found that after knocking out Smek1/2, the expression profiles of mRNAs and lncRNAs revealed significant changes. Analyses indicated that these affected mRNAs have connections with the pathway network for the differentiation and proliferation of NSCs. Furthermore, we performed a co-expression network analysis on the differentially expressed mRNAs and lncRNAs, which helped reveal the possible regulatory rules of lncRNAs during the differentiation after knocking out Smek1/2. Conclusion: By comparing group WT with KO, we found 366 differentially expressed mRNAs and 12 lncRNAs. GO and KEGG enrichment analysis on these mRNAs suggested their relationships with differentiation and proliferation of NSCs. Some of these mRNAs and lncRNAs have been verified to play regulatory roles in nervous system. Analyses on the co-expression network also indicated the possible functions of affected mRNAs and lncRNAs during NSCs differentiation after knocking out Smek1/2.