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.
Highlights
Circular RNAs have recently been found to be expressed in human brain tissue, and many lines ofevidence indicate that circular RNA (circRNA) play regulatory roles in neurodevelopment
CircRNAsare abundant and highly expressed in neural stem cells (NSCs) differentiation Total RNA was collected from mouse NSCs cultured in differentiation-suppressed medium or induced to differentiation with two replicates (Fig. 1)
In the 2d.nsc group, NSCs were first kept undifferentiated in 4 days and induced to differentiation in 2 days without adding bFGF.And in the 6d.nsc group, NSCs were induced at the beginning of culturing and were kept in differentiation state in 6 days
Summary
Circular 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. Investigators found that while most circRNAs are inlow expression level, they are conserved and expressed in a time-, cell type- andgene-specific manner [14]. Cognate genesrefer to those linear genes have the same sequences with circRNAs. Some circRNAs are present at higher copynumbers when compared to their cognate genes (> 10-fold) [15].So far, the function of most circRNAshas still been elusive. Functional studies have been reported in literature, investigation ofcircRNA’sfunction in neural tissue has not been systematically done yet
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