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一种新型长链非编码RNA lnc158通过靶向核因子-κB促进小鼠神经前体细胞向少突胶质细胞分化。

A novel long noncoding RNA lnc158 promotes the differentiation of mouse neural precursor cells into oligodendrocytes by targeting nuclear factor-IB.

作者信息

Li Yalei, Guo Baosen, Yang Rong, Xiao Zengrong, Gao Xuehu, Yu Jinjun, Li Siguang, Luo Yuping

机构信息

College of Life Sciences, Nanchang University, Nanchang.

Department of Regenerative Medicine, Stem Cell Center, Tongji University School of Medicine, Shanghai, China.

出版信息

Neuroreport. 2018 Sep 5;29(13):1121-1128. doi: 10.1097/WNR.0000000000001083.

DOI:10.1097/WNR.0000000000001083
PMID:29965871
Abstract

Long noncoding RNAs have been implicated in oligodendrocyte myelination and oligodendrocyte maturation, but their roles in normal oligodendrocyte differentiation are not fully defined. Here, we report a novel nonprotein-coding RNA, named lnc158, discovered in mouse oligodendrocytes identified in subependymal ventricular zone tissue by single-cell RNA sequencing. Lnc158 is an endogenous antisense transcript of nuclear factor-IB (NFIB) and complementary to 3' untranslated region of NFIB mRNA. NFIB is a member of the nuclear factor-I family and is essential in the development of many organs such as brains and lungs. We found that lnc158 transcripts serve a biological function by regulating the transcription level of the NFIB coding gene in neural stem cells. Overexpression of lnc158 increased the expression of NFIB mRNA and knockdown of lnc158 decreased the expression of NFIB mRNA, suggesting that NFIB is regulated positively by lnc158. Further analyses showed that overexpression of lnc158 in neural stem cells induced a modest increase in CNP, MBP, MAG, and OSP mRNA level, and enhanced induction of differentiation along the lineage of oligodendrocytes. These results together imply that lnc158 positively modulates the transcription level of NFIB mRNA, leading to the enhanced induction of oligodendrocytes.

摘要

长链非编码RNA已被证明与少突胶质细胞髓鞘形成和少突胶质细胞成熟有关,但其在正常少突胶质细胞分化中的作用尚未完全明确。在此,我们报告了一种新的非蛋白质编码RNA,名为lnc158,它是通过单细胞RNA测序在室管膜下区组织中鉴定出的小鼠少突胶质细胞中发现的。Lnc158是核因子-IB(NFIB)的内源性反义转录本,与NFIB mRNA的3'非翻译区互补。NFIB是核因子-I家族的成员,在许多器官如脑和肺的发育中至关重要。我们发现lnc158转录本通过调节神经干细胞中NFIB编码基因的转录水平发挥生物学功能。lnc158的过表达增加了NFIB mRNA的表达,而lnc158的敲低降低了NFIB mRNA的表达,这表明lnc158对NFIB起正向调节作用。进一步分析表明,lnc158在神经干细胞中的过表达导致CNP、MBP、MAG和OSP mRNA水平适度增加,并增强了沿少突胶质细胞谱系的分化诱导。这些结果共同表明,lnc158正向调节NFIB mRNA的转录水平,导致少突胶质细胞的诱导增强。

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