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

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.