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

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Author(s): Qichang Yang, Jing Wu, Jian Zhao, Tianyi Xu, Ping Han*, Xiaofeng Song*.

Journal Name: Current Bioinformatics

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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 prevented NSCs from differentiation, thus to affect the development of nervous system. In recent years, the important roles of lncRNAs in regulating numerous developmental and biological pathways had been implicated. However, the effects of knocking out Smek on the expression profiles of lncRNAs during the differentiation remain unknown.

RESULTS: In this study, we obtained NSCs from the C57BL/6J mouse fetal cerebral cortex. One group of NSCs were from wildtype mouse (WT group), while another group was from knocked out Smek1/2 (KO group). We extracted total RNA from both two groups in different differentiation time points and then performed RNA sequencing. By analyzing the RNA-Seq data, we found that after knocking out Smek1/2, the expression profiles of mRNAs and lncRNAs were changed largely. GO and KEGG enrichment analysis indicated that the pathway network for the differentiation and proliferation of NSCs were affected. Furthermore, we performed a co-expression network analysis for the differentially expressed mRNAs and lncRNAs. The result exhibited defects in nervous system using GO and KEGG, which indicated the influences of Smek1/2 on lncRNAs during the NSCs differentiation.

CONCLUSION: By comparing group WT versus KO, we found 366 differentially expressed mRNAs and 12 lncRNAs. Some of these mRNAs and lncRNAs have regulatory roles in nervous system, which indicated the influences of knocking out Smek1/2 on lncRNAs during the NSCs differentiation. GO and KEGG enrichment analysis on these mRNAs also suggested Smek1/2 had affected differentiation and proliferation during NSCs differentiation. The co-expression network is consistent with the change of expression profiles between the group WT versus KO, suggesting that the key lncRNAs had affected NSCs differentiation.

Keywords: lncRNA; expression profile; Smek; neural stem cell; differentiation

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(E-pub Abstract Ahead of Print)
DOI: 10.2174/1574893614666190308160507
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