Transcriptional Profiling of Ligand Expression in Cell Specific Populations of the Adult Mouse Forebrain That Regulates Neurogenesis.

Transcriptional Profiling of Ligand Expression in Cell Specific Populations of the Adult Mouse Forebrain That Regulates Neurogenesis.
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DOI:
10.3389/fnins.2018.00220
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发表时间:
2018
影响因子:
4.3
通讯作者:
Küry P
Küry P
中科院分区:
医学2区
文献类型:
--
作者:
Azim K;Akkermann R;Cantone M;Vera J;Jadasz JJ;Küry P

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在成人中枢神经系统(CNS)中,前脑的脑室下区(SVZ)是神经干细胞(NSCs)的最大和最活跃的来源,其主要产生神经元和少量胶质细胞终身。大量的证据揭示了信号配体的不同家族(即,形态发生素、生长因子、改变信号传导途径的分泌分子)在调节NSC生物学中的作用。然而,大多数研究集中在单个或少数信号配体及其通路组分在神经发生背景下的CNS特定细胞类型中的mRNA表达。一个单一的统一的研究,强调这种分子的表达,全面在不同的细胞类型中的空间背景尚未报道。通过使用成年CNS、SVZ龛、NSC、神经胶质细胞、脉络丛的单个纯化细胞特异性群体的全基因组转录组数据集,并进行信号传导配体的生物信息学荟萃分析,揭示了它们在前脑中的表达。其中,我们报告了大量配体在SVZ利基中大量表达,主要来自血管系统,而不是来自可能调节神经发生的其他来源。有趣的是,这种分析揭示了许多在神经发生背景下具有未知功能的配体,值得进一步研究。因此,这项研究为该领域的研究人员提供了一个框架,以了解信号配体的表达模式和调节神经发生的途径。
In the adult central nervous system (CNS), the subventricular zone (SVZ) of the forebrain is the largest and most active source of neural stem cells (NSCs) that generates mainly neurons and few glial cells lifelong. A large body of evidence has shed light on the distinct families of signaling ligands (i.e., morphogens, growth factors, secreted molecules that alter signaling pathways) in regulating NSC biology. However, most of the research has focused on the mRNA expression of individual or few signaling ligands and their pathway components in specific cell types of the CNS in the context of neurogenesis. A single unifying study that underlines the expression of such molecules comprehensively in different cell types in spatial contexts has not yet been reported. By using whole genome transcriptome datasets of individual purified cell specific populations of the adult CNS, the SVZ niche, NSCs, glial cells, choroid plexus, and performing a bioinformatic meta-analysis of signaling ligands, their expression in the forebrain was uncovered. Therein, we report that a large plethora of ligands are abundantly expressed in the SVZ niche, largely from the vasculature than from other sources that may regulate neurogenesis. Intriguingly, this sort of analysis revealed a number of ligands with unknown functions in neurogenesis contexts that warrants further investigations. This study therefore serves as a framework for investigators in the field for understanding the expression patterns of signaling ligands and pathways regulating neurogenesis.
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