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.

背景：以前的研究表明，分化后神经干细胞（NSCs）的细胞命运是由Smek1（一种Mek null抑制子（Smek）的同工型）决定的。Smek缺乏会阻止NSC分化，从而影响神经系统的发育。近年来，已发现lncRNA参与许多发育和生物学途径。然而，在分化过程中敲除Smek对lncRNAs表达谱的影响仍然未知。

目的：本研究旨在探讨lncRNA的表达谱及其在Smek1 / 2基因敲除的NSCs分化过程中的可能功能。

方法：我们从C57BL / 6J小鼠胎儿大脑皮层中获得了NSC。一组NSC来自野生型小鼠（野生型组），另一组来自基因敲除的Smek1 / 2（KO组）。

结果：通过分析RNA-Seq数据，我们发现敲除Smek1 / 2后，mRNA和lncRNA的表达谱显示出显着变化。分析表明，这些受影响的mRNA与NSCs分化和增殖的通路网络有关。此外，我们对差异表达的mRNA和lncRNA进行了共表达网络分析，这有助于揭示敲除Smek1 / 2后分化过程中lncRNA的可能调控规则。

结论：通过比较WT组和KO组，我们发现了36​​6个差异表达的mRNA和12个lncRNA。对这些mRNA的GO和KEGG富集分析表明它们与NSC的分化和增殖有关。这些mRNA和lncRNA中的某些已被证实在神经系统中起调节作用。对共表达网络的分析还表明，敲除Smek1 / 2后，在NSC分化过程中受影响的mRNA和lncRNA可能具有功能。