SOX10-Mediated Regulation of Enteric Glial Phenotype in vitro and its Relevance for Neuroinflammatory Disorders

IF 2.7 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Madlen Kunke, Meike Kaehler, Sebastien Boni, Katja Schröder, Alicia Weier, Rittika Chunder, Stefanie Kuerten, Martina Böttner, Ingolf Cascorbi, Michel Neunlist, Thilo Wedel, Ralph Lucius, François Cossais
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引用次数: 0

Abstract

The transcription factor SOX10 is a key regulator of myelinated glial cell phenotype and function, with a known role in multiple sclerosis (MS). SOX10 is also expressed in enteric glial cells (EGC) within the gut, yet its regulatory functions in EGC remain poorly understood. This study aimed to identify SOX10 target genes that influence EGC phenotype and may have implications for MS. An EGC cell line was established for doxycycline-inducible SOX10 overexpression. Impact of SOX10 overexpression on EGC phenotype was assessed by genome-wide expression analysis and results were validated via RT-qPCR and western blot. Data were compared with SOX10 ChIP-seq and transcriptomic datasets from MS patients to identify pan-glial SOX10 target genes potentially linked to neuroinflammatory disorders. SOX10 overexpression was associated with ectopic upregulation of genes related to myelin regulation and glial differentiation, as evidenced by increased PLP1 expression at mRNA and protein levels. Comparison to ChIP-seq and MS datasets highlight SOX10 target genes, including PLP1, RNF130, NES and APOD potentially involved in central and peripheral manifestations of MS pathology. Our findings support a cell-specific regulation of EGC phenotype through SOX10 expression level and identify SOX10-regulated genes relevant to EGC function. This research advances the understanding of EGC diversity and provide information about glial cells targeting in neuroinflammatory disorders.

sox10介导的体外肠胶质细胞表型调控及其与神经炎性疾病的相关性
转录因子SOX10是髓鞘胶质细胞表型和功能的关键调节因子,在多发性硬化症(MS)中起着已知的作用。SOX10也在肠内的肠胶质细胞(EGC)中表达,但其在EGC中的调节功能尚不清楚。本研究旨在鉴定影响EGC表型并可能与ms相关的SOX10靶基因,建立了多西环素诱导SOX10过表达的EGC细胞系。通过全基因组表达分析评估SOX10过表达对EGC表型的影响,并通过RT-qPCR和western blot验证结果。将数据与MS患者的SOX10 ChIP-seq和转录组学数据集进行比较,以鉴定可能与神经炎性疾病相关的泛胶质SOX10靶基因。SOX10过表达与髓磷脂调控和胶质细胞分化相关基因的异位上调有关,PLP1 mRNA和蛋白水平的表达增加证明了这一点。与ChIP-seq和MS数据集的比较突出了SOX10靶基因,包括PLP1、RNF130、NES和APOD,这些基因可能参与MS病理的中枢和外周表现。我们的研究结果支持通过SOX10表达水平对EGC表型进行细胞特异性调节,并鉴定出与EGC功能相关的SOX10调节基因。本研究促进了对EGC多样性的理解,并提供了神经炎性疾病中胶质细胞靶向的信息。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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