Circular RNA expression profiles during the differentiation of mouse neural stem cells

Abstract

BackgroundCircular RNAs (circRNAs) have recently been found to be expressed in human brain tissue, and many lines ofevidence indicate that circRNAs play regulatory roles in neurodevelopment. Proliferation and differentiation of neural stem cells (NSCs) are critical parts during development of central nervous system (CNS).To date, there have been no reports ofcircRNA expression profiles during the differentiation of mouse NSCs. We hypothesizethat circRNAs mayregulate gene expression in the proliferation anddifferentiation of NSCs.ResultsIn this study, we obtained NSCs from the wild-type C57BL/6 J mouse fetal cerebral cortex. We extracted total RNA from NSCs in different differentiation stagesand then performed RNA-seq. By analyzing the RNA-Seq data, we found 37circRNAs and 4182 mRNAs differentially expressedduringthe NSC differentiation. Gene Ontology (GO) enrichment analysis of thecognate linear genes of these circRNAsrevealed that some enriched GO terms were related to neural activity. Furthermore, we performed a co-expression network analysis of these differentially expressed circRNAs and mRNAs. The result suggested a stronger GO enrichmentin neural features for both the cognate linear genes of circRNAs and differentially expressed mRNAs.ConclusionWe performed the first circRNA investigation during the differentiation of mouse NSCs. Wefound that12 circRNAs might have regulatory roles duringthe NSC differentiation, indicating that circRNAs might be modulated during NSC differentiation.Our network analysis suggested the possible complex circRNA-mRNA mechanisms during differentiation, and future experimental workis need to validate these possible mechanisms.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0651-1) contains supplementary material, which is available to authorized users.

Translation and functional roles of circular RNAs in human cancer

“…CircRNAs are generally expressed in vast majority of human tissues and are especially highly expressed in human brain [18,40]. Furthermore, the expression of circRNAs always has a tissue-or cellspecific manner, which makes them a suitable candidate for biomarker studies in human cancer [10,19,20,41].…”

“…High-throughput technologies have enabled in-depth characterization of circRNAs for identification and potential functions [15][16][17], such as ribosomal RNA depleted RNA sequencing, long-read sequencing and more importantly, improved circRNA mining bioinformatics algorithms. CircRNAs have been demonstrated as an abundant and conserved class of RNAs, and are widely expressed in a complex tissue-, cell type-or stagespecific manner [10,[18][19][20][21][22]. Recent studies confirmed the significant biological functions of circRNAs, especially in human cancers [23,24].…”

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“…Neural stem cells (NSCs) existing in the subventricle zone of the brain's germinal region and the subgranular zone of the hippocampus are capable of self-renewing, proliferating, migrating, and differentiating into various types of cells within the brain and spinal cord tissue [13,41]. NSC differentiation into neurons, astrocytes, and oligodendrocytes could replace necrotic cells resulting from injuries to promote the structural and functional repair of the brain and spinal cord [50]. However, this self-renewal is not adequate for the recovery of neurological function after brain injury [1,32,47].…”

The International Conference on Intelligent Biology and Medicine (ICIBM) 2018: systems biology on diverse data types

“…The third paper by Yang et al [3] focused on systems biology of gene expression on a different type of transcripts, circular RNAs (circRNAs). There have been no reports of circRNAs expression profiles during the differentiation of mouse neural stem cells (NSCs) and the authors tried to find the possible regulatory roles of cir-cRNAs in the differentiation.…”