Differential long noncoding RNA and messenger RNA expression profiling and functional network analysis in stroke-induced neurogenesis

Abstract

Background and Purpose-Adult neurogenesis contributes to neurological recovery after stroke. Long non-coding RNAs (lncRNAs) play an important role in the self-renewal and differentiation of stem cells. However, knowledge of the lncRNAs in stroke-induced neurogenesis remains unclear. Methods and Results- In the study, we isolated adult neural stem cells (NSCs) from the subventricular zone (SVZ) neurogenic region of adult non-ischemic and ischemic rats subjected to 7 day middle cerebral artery occlusion and then performed lncRNA profile analysis. In total, 155 lncRNAs were found to be significantly differentially down-regulated, while 86 lncRNAs were significantly up-regulated after stroke. Also, we identified 409 mRNAs were significantly up-regulated and 255 were down-regulated in ischemic NSCs compared with non-ischemic NSCs. We found that 4 significantly upregulated lncRNAs and 2 downregulated lncRNAs were positively correlated with their neighboring coding genes. Furthermore, the network analysis revealed matched lncRNA-mRNA correlations. A gene set enrichment analysis (GSEA) showed that Gene ontology (GO) of targeted genes that were positively modulated by lncRNAs was mainly related to synapse plasticity, cognition, neuron development, mitochondria, neurotransmitter signaling, calcium channel regulation, etc. Meanwhile, co-expressed genes negatively regulated by lncRNAs were correlated with DNA replication, cytokine production, cell adhesion, $\text{NF}-\kappa\mathrm{B}$ signaling, T cell process, metabolic process, etc. Conclusions- The present study provides a comprehensive catalog of lncRNAs involved in the ischemic NSCs and provides new insight into understanding the role of lncRNAs in stroke-induced neurogenesis.