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该基因在人类神经祖细胞的神经元分化过程中影响细胞通路。

The Gene Influences Cellular Pathways in the Neuronal Differentiation of Human Neural Progenitor Cells.

作者信息

Kośla Katarzyna, Płuciennik Elżbieta, Styczeń-Binkowska Ewa, Nowakowska Magdalena, Orzechowska Magdalena, Bednarek Andrzej K

机构信息

Department of Molecular Carcinogenesis, Medical University of Łódź, Łódź, Poland.

出版信息

Front Cell Neurosci. 2019 Aug 30;13:391. doi: 10.3389/fncel.2019.00391. eCollection 2019.

Abstract

The brain is the most functionally organized structure of all organs. It manages behavior, perception and higher cognitive functions. The gene is non-classical tumor suppressor gene, which has been shown to have an impact on proliferation, apoptosis and migration processes. Moreover, genetic aberrations in induce severe neuropathological phenotypes in humans and rodents. The aim of the present study was to investigate in detail the impact of on human neural progenitor cell (hNPC) maintenance and how depletion of disturbs signaling pathways playing a pivotal role in neuronal differentiation and central nervous system (CNS) organogenesis. hNPC with a silenced gene exhibited lowered mitochondrial redox potential, enhanced adhesion to fibronectin and extracellular matrix protein mixture, downregulation of MMP2/9 expression and impaired 3D growth. Global transcriptome analysis using cap analysis of gene expression (CAGE) found that downregulation significantly changes the expression of multiple genes engaged in cytoskeleton organization, adhesion, cell signaling and chromatin remodeling. The massive changes in gene expression caused by silencing may strongly affect the differentiation and migration of neurons in organogenesis, brain injury, cancerogenesis or neurodifferentiation. gene appears to be an important regulator of neural tissue architecture and function.

摘要

大脑是所有器官中功能组织最为完善的结构。它掌管行为、感知和高级认知功能。该基因是非经典肿瘤抑制基因,已被证明对增殖、凋亡和迁移过程有影响。此外,该基因的遗传畸变在人类和啮齿动物中会引发严重的神经病理表型。本研究的目的是详细探究该基因对人神经祖细胞(hNPC)维持的影响,以及该基因缺失如何扰乱在神经元分化和中枢神经系统(CNS)器官发生中起关键作用的信号通路。沉默该基因的hNPC表现出线粒体氧化还原电位降低、对纤连蛋白和细胞外基质蛋白混合物的黏附增强、MMP2/9表达下调以及三维生长受损。使用基因表达帽分析(CAGE)进行的全转录组分析发现,该基因下调显著改变了多个参与细胞骨架组织、黏附、细胞信号传导和染色质重塑的基因的表达。该基因沉默引起的基因表达大量变化可能会强烈影响器官发生、脑损伤、肿瘤发生或神经分化过程中神经元的分化和迁移。该基因似乎是神经组织结构和功能的重要调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aeb/6730490/98cdf2847825/fncel-13-00391-g001.jpg

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