Identification, characterization, and functional investigation of circular RNAs in subventricular zone of adult rat brain
Identification, characterization, and functional investigation of circular RNAs in subventricular zone of adult rat brain
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成年大鼠脑室下区环状 RNA 的鉴定、表征和功能研究。
DOI：
10.1002/jcb.27614
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Qian，Ling-Jia
中科院分区：
文献类型：
--
作者：
Xie，Fang;Zhao，Yun;Qian，Ling-Jia
成体神经干细胞（NSCs）能够自我更新并产生新的神经细胞。确定NSCs的调节因子对于开发基于NSCs的神经退行性疾病和脑损伤治疗具有重要意义。近年来，环状rna （circRNAs）已在多种细胞系和脑组织中被表征，并被发现参与多种生物过程。然而，circRNAs在成人NSCs中的表达模式尚不清楚。本研究分离侧脑室下区（SVZ）作为成年大鼠脑中NSCs的生态位进行RNA测序，并研究SVZ区和大脑皮层的circRNAs谱特征。结果，在SVZ和皮层中分别鉴定出29 049和31 975个circrna。其中41例为SVZ特异性，48例为皮质特异性。467个circrna也主要在SVZ中表达，而皮层中有其他423个circrna。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析显示，SVZ特异性circRNAs与NSC扩增和NSC -生态位相互作用的调控密切相关，而其他差异表达的circRNAs可能参与神经细胞构建和神经系统功能。此外，研究人员还探索了circRNA和microrna之间的相互作用，结果表明，一种SVZ特异性circRNA能够竞争性地结合miR - 138 - 5p，作为NSCs增殖的潜在抑制调节剂。因此，我们的工作为破译成人NSCs中circRNAs的调控机制以及开发circRNAs作为成人NSCs的新型生物标志物奠定了基础。
Adult neural stem cells (NSCs) are able to self‐renew and generate new neural cells. Identifying regulators of NSCs is significant for the development of NSC‐based therapies for neurodegenerative diseases and brain injuries. Recently, circular RNAs (circRNAs) have been characterized in various cell lines and brain tissues, and found to participate in multiple biological processes. However, the expression pattern of circRNAs in adult NSCs is still unknown. Here, the subventricular zone (SVZ) of the lateral ventricle was isolated as the niche of NSCs in adult rat brain for RNA sequencing and the characteristics of circRNAs profiling in both SVZ and cerebral cortex were also investigated. As a result, 29 049 and 31 975 circRNAs were identified in SVZ and cortex, respectively. Among them, 41 were SVZ‐specific and 48 were cortex‐specific. 467 circRNAs were also found to express predominately in SVZ, while the cortex had other 423 circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the SVZ‐specific circRNAs have close relationship with the regulation of NSC expansion and NSC‐niche interaction, while the other differentially expressed circRNAs might be involved in neural cellular construction and nerve system function. Furthermore, the interactions between circRNAs and microRNAs were also explored, and the result showed that one SVZ‐specific circRNA was capable to competitively bind miR‐138‐5p as a potential derepressive regulator in NSCs proliferation. Hence, our work has laid the foundations to decipher regulation mechanisms of circRNAs in adult NSCs and to develop circRNAs as novel biomarkers for adult NSCs.